\\n\\n
IntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
\\n\\nIntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
\\n\\nLaunching 2021
\\n\\nArtificial Intelligence, ISSN 2633-1403
\\n\\nVeterinary Medicine and Science, ISSN 2632-0517
\\n\\nBiochemistry, ISSN 2632-0983
\\n\\nBiomedical Engineering, ISSN 2631-5343
\\n\\nInfectious Diseases, ISSN 2631-6188
\\n\\nPhysiology (Coming Soon)
\\n\\nDentistry (Coming Soon)
\\n\\nWe invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
\\n\\nNote: Edited in October 2021
\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/132"}},components:[{type:"htmlEditorComponent",content:'With the desire to make book publishing more relevant for the digital age and offer innovative Open Access publishing options, we are thrilled to announce the launch of our new publishing format: IntechOpen Book Series.
\n\nDesigned to cover fast-moving research fields in rapidly expanding areas, our Book Series feature a Topic structure allowing us to present the most relevant sub-disciplines. Book Series are headed by Series Editors, and a team of Topic Editors supported by international Editorial Board members. Topics are always open for submissions, with an Annual Volume published each calendar year.
\n\nAfter a robust peer-review process, accepted works are published quickly, thanks to Online First, ensuring research is made available to the scientific community without delay.
\n\nOur innovative Book Series format brings you:
\n\nIntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
\n\nIntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
\n\nLaunching 2021
\n\nArtificial Intelligence, ISSN 2633-1403
\n\nVeterinary Medicine and Science, ISSN 2632-0517
\n\nBiochemistry, ISSN 2632-0983
\n\nBiomedical Engineering, ISSN 2631-5343
\n\nInfectious Diseases, ISSN 2631-6188
\n\nPhysiology (Coming Soon)
\n\nDentistry (Coming Soon)
\n\nWe invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
\n\nNote: Edited in October 2021
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"6658",leadTitle:null,fullTitle:"Stromal Cells - Structure, Function, and Therapeutic Implications",title:"Stromal Cells",subtitle:"Structure, Function, and Therapeutic Implications",reviewType:"peer-reviewed",abstract:"Stromal cells are connective tissue cells of any organ, and they support the function of the parenchymal cells of that particular organ. Stromal/stromal stem cells are fundamentally a heterogeneous population of cells with contradictory differentiation potential depending upon their environmental niche. Stromal cell biology is not only intriguing, but equally stromal cell ontogeny in vivo remains challenging. In recent years there has been substantial advances in our understanding of stromal cell biology, especially stromal cell isolation, characterization, differentiation, and interactions in physiological (epithelial-stromal interactions) as well as pathophysiological (stromal-cancer interactions) contexts. In addition, stromal cells are also utilized more and more as a therapeutic tool not only in the field of gene therapy but also in the translational field of tissue engineering and regenerative medicine. Therefore, the goal of this book is to consolidate the recent advances in the area of stromal/stromal stem cell biology covering a broad range of interrelated topics in a timely fashion and to disseminate that knowledge in a lucid way to a greater scientific audience. This book will prove highly useful for students, researchers, and clinicians in stem cell biology, developmental biology, cancer biology, pathology, oncology, as well as tissue engineering and regenerative medicine. This quick reference will benefit anyone desiring a thorough overview of stromal cell structure, function, and its therapeutic implications.",isbn:"978-1-78984-985-1",printIsbn:"978-1-78984-984-4",pdfIsbn:"978-1-83881-624-7",doi:"10.5772/intechopen.71899",price:119,priceEur:129,priceUsd:155,slug:"stromal-cells-structure-function-and-therapeutic-implications",numberOfPages:260,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"c215f02d4268e4b7cccdaea141ec8647",bookSignature:"Mani T. Valarmathi",publishedDate:"January 23rd 2019",coverURL:"https://cdn.intechopen.com/books/images_new/6658.jpg",numberOfDownloads:12840,numberOfWosCitations:15,numberOfCrossrefCitations:12,numberOfCrossrefCitationsByBook:1,numberOfDimensionsCitations:30,numberOfDimensionsCitationsByBook:1,hasAltmetrics:0,numberOfTotalCitations:57,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 27th 2017",dateEndSecondStepPublish:"December 18th 2017",dateEndThirdStepPublish:"February 16th 2018",dateEndFourthStepPublish:"May 7th 2018",dateEndFifthStepPublish:"July 6th 2018",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"69697",title:"Dr.",name:"Mani T.",middleName:null,surname:"Valarmathi",slug:"mani-t.-valarmathi",fullName:"Mani T. Valarmathi",profilePictureURL:"https://mts.intechopen.com/storage/users/69697/images/system/69697.jpg",biography:"Mani T. Valarmathi is currently Director of Research and Development at Religen Inc., a life science company in Pennsylvania, USA. He began his scientific career as a cancer geneticist but soon became captivated with the emerging and translational fields of stem cell biology, tissue engineering, and regenerative medicine. After obtaining a bachelor’s degree in Chemistry from the University of Madras, Chennai, Tamil Nadu, India, he obtained an MBBS in Medicine and Surgery and an MD in Pathology from the same university. Dr. Valarmathi also holds a Ph.D. in Medical Biotechnology from the All-India Institute of Medical Sciences, New Delhi, India. Over the past two decades, he has had extensive experience in research on various types of stem cells, focused on creating bioengineered human 3D vascularized tissues constructs for implantation purposes. At present, much of his research is directed towards developing innovative molecular genetic testing for precision and genetic medicine. He is a member of many prestigious national and international professional societies and scientific organizations, including the International Society for Stem Cell Research (ISSCR), Tissue Engineering and Regenerative Medicine International Society (TERMIS), American Association for Cancer Research (AACR), American Society for Investigative Pathology (ASIP), American Society for Clinical Pathology (ASCP), American Chemical Society (ACS), European Society of Cardiology (ESC), International Society for Heart Research (ISHR), American Society of Gene & Cell Therapy (ASGCT), and American Heart Association (AHA).",institutionString:"Religen Inc. | A Life Science Company, United States of America",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"4",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"990",title:"Stem Cell Research",slug:"medicine-cell-biology-stem-cell-research"}],chapters:[{id:"61988",title:"Stromal Stem Cells: Nature, Biology and Potential Therapeutic Applications",doi:"10.5772/intechopen.77346",slug:"stromal-stem-cells-nature-biology-and-potential-therapeutic-applications",totalDownloads:1055,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Stromal cells are connective tissue cells of any organ. Mesenchymal stromal cells (MSCs), are multipotent progenitors, which were first described by Caplan and colleagues in 1991. MSCs hold great potential for regenerative medicine because of their ability for self-renewal and differentiation into tissue-specific cells such as osteoblasts, chondrocytes, and adipocytes. Recent studies indicate that MSCs resemble pericytes and emerge from the peripheral stromal region surrounding blood vessels, thus clarifying their broad regenerative potential in adult tissues. The development of uniform protocols for both preparation and characterization of MSCs, including standardized functional assays for evaluation of their biological potential, are critical factors contributing to their clinical utility. Nowadays, due to the capacity of modulating immunological responses, supporting hematopoiesis and repairing tissues, MSCs have been widely used to treat immune-based disorders, such as Crohn’s disease, rheumatoid arthritis, diabetes, and multiple sclerosis. Based on animal experiments and clinical studies, the most successful clinical application of MSCs is in the field of hematological disease.",signatures:"Amira Hassouna, Marwa M. Abd Elgwad and Hoda Fahmy",downloadPdfUrl:"/chapter/pdf-download/61988",previewPdfUrl:"/chapter/pdf-preview/61988",authors:[{id:"239276",title:"Prof.",name:"Amira",surname:"Hassouna",slug:"amira-hassouna",fullName:"Amira Hassouna"},{id:"239999",title:"Dr.",name:"Marwa",surname:"Abdelgwad",slug:"marwa-abdelgwad",fullName:"Marwa Abdelgwad"},{id:"240000",title:"BSc.",name:"Hoda",surname:"Fahmy",slug:"hoda-fahmy",fullName:"Hoda Fahmy"}],corrections:null},{id:"62246",title:"Stromal Cell Ultrastructure",doi:"10.5772/intechopen.76870",slug:"stromal-cell-ultrastructure",totalDownloads:1093,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Regenerative medicine and tissue engineering therapies present an attractive treatment alternative to the current traditional clinical treatments. Stem cells are capable of self-renewal and multilineage differentiation. They also have the ability to create immunomodulatory microenvironment, and thus help to minimize organ damage caused by the inflammation and cells activated by the immune system. Human bone marrow mesenchymal stem/stromal cells (MSCs) have great potential for cellular therapy, as they possess the abilities to proliferate as well as to differentiate. MSCs are present in all tissues interacting with tissue cells and easy to isolate and expand in culture. Indeed, histological examination of MSCs is one of the main goals for studying their morphology. Both the light and the electron microscopes are essential tools where the histologist can identify the structure as well as the detailed ultrastructure of these cells. This will guide users to clearly understand their behavior, both in vivo and in vitro. Thus, the aim of this chapter is to give a spot of light on these cells and their histology.",signatures:"Amany A. Moneim Solaiman",downloadPdfUrl:"/chapter/pdf-download/62246",previewPdfUrl:"/chapter/pdf-preview/62246",authors:[{id:"237379",title:"Prof.",name:"Amany",surname:"Solaiman",slug:"amany-solaiman",fullName:"Amany Solaiman"}],corrections:null},{id:"61053",title:"Adult Stem Cell Membrane Markers: Their Importance and Critical Role in Their Proliferation and Differentiation Potentials",doi:"10.5772/intechopen.76869",slug:"adult-stem-cell-membrane-markers-their-importance-and-critical-role-in-their-proliferation-and-diffe",totalDownloads:1338,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The stem cells are part of the cells that belong to the stromal tissue. These cells remain in a quiescent state until they are activated by different factors, usually those generated by an alteration in the parenchymal tissue. These cells have characteristic membrane markers such as CD73, CD90, and CD105. Those are a receptor, which in response to their ligand induces strong changes in different metabolic pathways that lead to these cells, both to generate molecules with different activities and to leave their stationary phase to reproduce and even differentiate. This review describes the metabolic pathways dependent on these membrane markers and how they influence on parenchymal tissue and other stromal cells.",signatures:"Maria Teresa Gonzalez Garza",downloadPdfUrl:"/chapter/pdf-download/61053",previewPdfUrl:"/chapter/pdf-preview/61053",authors:[{id:"181389",title:"Ph.D.",name:"Maria Teresa",surname:"Gonzalez Garza",slug:"maria-teresa-gonzalez-garza",fullName:"Maria Teresa Gonzalez Garza"}],corrections:null},{id:"63314",title:"Multipotent Stromal Cells in a Tumor Microenvironment",doi:"10.5772/intechopen.77345",slug:"multipotent-stromal-cells-in-a-tumor-microenvironment",totalDownloads:1173,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Multipotent mesenchymal stromal cells [also referred to as mesenchymal stem cells (MSCs)] as was previously described, are a heterogeneous subset of stromal cells with regenerative potential. Their present tropism for inflamed sites including tumors lesion may be adverse or therapeutic effects arising from MSC administration; in this context, their potential for producing trophic and immunomodulatory factors raises the question as to whether MSCs promote or interact with a tumor microenvironment. Previous studies show a paradoxical effect regarding MSCs, which seems to depend on isolation and expansion, cells source, dose and both route and timing of administration. The occurrence of neoplastic transformation in ex vivo expanded MSCs after a long-term culture has been reported, however, this event has been subsequently described as uncommon, with an estimated frequency of <10−9. Furthermore, neither ectopic tissue formation nor MSC-originating tumors have ever been reported so far in hundreds of patients treated with MSC therapy. The biosafety of these cells, both in precancerous and cancerous environments, has been little investigated to date. We found in an animal model of oral cancer that locally or systemically administered allogeneic MSCs do not aggravate the progression of precancerous lesions. Moreover, they preclude cancer progression and tumor growth, particularly at papilloma stage.",signatures:"Flavia Alejandra Bruna",downloadPdfUrl:"/chapter/pdf-download/63314",previewPdfUrl:"/chapter/pdf-preview/63314",authors:[{id:"231261",title:"Ph.D.",name:"Flavia Alejandra",surname:"Bruna",slug:"flavia-alejandra-bruna",fullName:"Flavia Alejandra Bruna"}],corrections:null},{id:"63044",title:"Stromal-Epithelial Interactions during Mammary Gland Development",doi:"10.5772/intechopen.80405",slug:"stromal-epithelial-interactions-during-mammary-gland-development",totalDownloads:1415,totalCrossrefCites:2,totalDimensionsCites:7,hasAltmetrics:0,abstract:"Mammary gland is an organ, which undergoes the majority of its development in the postnatal life of mammals. The complex structure of the mammary gland comprises epithelial and myoepithelial cells forming the parenchymal tissue and adipocytes, fibroblasts, vascular endothelial cells, and infiltrating immune cell composing the stromal compartment. During puberty and in adulthood, circulating hormones released from the pituitary and ovaries regulate the rate of development and functional differentiation of the mammary epithelium. In addition, growing body of evidence shows that interactions between the stromal and parenchymal compartments of the mammary gland play a crucial role in mammogenesis. This regulation takes place on a paracrine level, by locally synthesized growth factors, adipokines, and cytokines, as well as via direct cell-cell interactions. This chapter summarizes the current knowledge about the complex nature of interactions between the mammary epithelium and stroma during mammary gland development in different mammalian species.",signatures:"Żaneta Dzięgelewska and Małgorzata Gajewska",downloadPdfUrl:"/chapter/pdf-download/63044",previewPdfUrl:"/chapter/pdf-preview/63044",authors:[{id:"165068",title:"Dr.",name:"Malgorzata",surname:"Gajewska",slug:"malgorzata-gajewska",fullName:"Malgorzata Gajewska"},{id:"249847",title:"Ms.",name:"Żaneta",surname:"Dzięgelewska",slug:"zaneta-dziegelewska",fullName:"Żaneta Dzięgelewska"}],corrections:null},{id:"61441",title:"Molecular Aberrations in Bone Marrow Stromal Cells in Multiple Myeloma",doi:"10.5772/intechopen.77179",slug:"molecular-aberrations-in-bone-marrow-stromal-cells-in-multiple-myeloma",totalDownloads:1167,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Multiple myeloma (MM) is a B-cell malignancy characterized by an accumulation of malignant plasma cells within the bone marrow. Bone marrow mesenchymal stromal cells (BMMSCs) represent a crucial component of MM microenvironment supporting its progression and proliferation. Alterations in BMMSC of MM (MM-BMMSC) have become an important research focus. In this study, we analyzed MM-BMMSC and their modification through interaction with plasma cells in 128 MM patients. MM-BMMSC displayed a senescence-like state that was accompanied by an increase in senescence-associated β-galactosidase activity, a reduced number of colony-forming units, an accumulation of cells in S phase of the cell cycle, and the overexpression of microRNAs (miR-16, miR-223, miR-485-5p, and miR-519d) and p21. MM-BMMSC showed a reduced expression of mitochondrial stress response protein SIRT3 and an increased mitochondrial DNA mass that led to a higher amount of reactive oxygen species compared to healthy donor BMMSC. The interaction between MM cells and MM-BMMSC is a complex mechanism that relies on multiple interacting signaling pathways. Observed aberrations in MM-BMMSC should be confirmed in an in vivo model in order to clarify the importance for the pathogenesis of MM. Eventually, the result of MM therapy could be improved by understanding the interaction between MM cells and MM-BMSCs.",signatures:"Olga Blau, Rimma Berenstein, Marlies Wächter, Axel Nogai, Aline\nKünel, Mirgul Bayanova and Igor Wolfgang Blau",downloadPdfUrl:"/chapter/pdf-download/61441",previewPdfUrl:"/chapter/pdf-preview/61441",authors:[{id:"64876",title:"Dr.",name:"Olga",surname:"Blau",slug:"olga-blau",fullName:"Olga Blau"},{id:"235638",title:"Dr.",name:"Rimma",surname:"Berenstein",slug:"rimma-berenstein",fullName:"Rimma Berenstein"},{id:"235640",title:"Dr.",name:"Axel",surname:"Nogai",slug:"axel-nogai",fullName:"Axel Nogai"},{id:"236425",title:"Mrs.",name:"Marlies",surname:"Waechter",slug:"marlies-waechter",fullName:"Marlies Waechter"},{id:"236427",title:"Prof.",name:"Igor Wolfgang",surname:"Blau",slug:"igor-wolfgang-blau",fullName:"Igor Wolfgang Blau"},{id:"236444",title:"Dr.",name:"Mirgul",surname:"Bayanava",slug:"mirgul-bayanava",fullName:"Mirgul Bayanava"},{id:"255247",title:"Dr.",name:"Aline",surname:"Kuehnel",slug:"aline-kuehnel",fullName:"Aline Kuehnel"}],corrections:null},{id:"61954",title:"Mesenchymal Stromal Cells as a Therapeutic Intervention",doi:"10.5772/intechopen.78586",slug:"mesenchymal-stromal-cells-as-a-therapeutic-intervention",totalDownloads:1390,totalCrossrefCites:0,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Mesenchymal stem cells, also known as mesenchymal stromal cells (MSCs), are a safe and promising biologic therapeutic for inducing tissue repair and regeneration in a broad array of chronic diseases. The mechanisms underlying the beneficial effects of MSCs include immunomodulation, reduction in inflammation and fibrosis, and stimulation of neovascularization and endogenous regeneration. Accumulating evidence from a multitude of clinical trials support the notion that both autologous and allogeneic MSCs are not only safe but also possess the capacity for repair of diverse organ systems and amelioration of multiple chronic disease processes. However, there are many questions regarding the underlying mechanisms of action, the most efficacious cell characteristics, tissue source, dose/concentration, route of delivery, and timing of administration, interactions with concurrent therapies, sustainability of effect, donor and patient characteristics, and adverse effects, including infections and malignancy, that remain to be resolved. Answering these questions will require well-designed and rigorously conducted multicenter clinical trials with well-established and defined clinical endpoints and appropriately defined patient populations, number of patients, and duration of follow-up. This chapter will review the current state of knowledge in the use of MSCs as a therapeutic strategy for organ structural and functional repair in chronic diseases.",signatures:"Ivonne Hernandez Schulman and Joshua M. Hare",downloadPdfUrl:"/chapter/pdf-download/61954",previewPdfUrl:"/chapter/pdf-preview/61954",authors:[{id:"47873",title:"Dr.",name:"Ivonne",surname:"Schulman",slug:"ivonne-schulman",fullName:"Ivonne Schulman"},{id:"200961",title:"Dr.",name:"Joshua",surname:"Hare",slug:"joshua-hare",fullName:"Joshua Hare"}],corrections:null},{id:"61652",title:"Therapeutic Strategies of Secretome of Mesenchymal Stem Cell",doi:"10.5772/intechopen.78092",slug:"therapeutic-strategies-of-secretome-of-mesenchymal-stem-cell",totalDownloads:1315,totalCrossrefCites:1,totalDimensionsCites:4,hasAltmetrics:0,abstract:"Great progress has been made in the therapeutic strategies of multiple diseases that lack curative treatments with the transplantation of mesenchymal stem cells (MSC), such as in onco-hematological diseases, myocardial infarction (MI), cerebrovascular diseases, degenerative diseases of the nervous system (multiple sclerosis, Alzheimer’s disease), and diseases of the immune system, among others. Stem cells (SC) participate in the biological processes of tissue regeneration and repair through cell replication. Recently, the beneficial therapeutic effects of SCs that are generated by the release of proteins with paracrine actions and not by cell differentiation are more well known, and 80% of the therapeutic effect of SC is attributed to paracrine actions. The MSCs release large amounts of proteins and growth factors (GF), nucleic acids, proteasomes, exosomes, and microRNA, and membrane vesicles known as the secretome are released into the extracellular space, regulating multiple biological processes. Currently, the therapeutic strategies in tissue engineering (TE) and regenerative medicine (RM) are focused on the management of products derived from cells that act, both locally and remotely, in the affected tissue or organ, achieving regenerative actions. The application of new knowledge of the secretome initiates a change in the paradigm of regenerative therapy by knowing more about and using cell products derived from cells as a “factory” for biological drugs.",signatures:"Daniel Ascencio González, Rogelio Hernández Pando, Miguel Ángel\nGómez Lim, Sergio Ayala Fraustro and Aaron Torres Garcia",downloadPdfUrl:"/chapter/pdf-download/61652",previewPdfUrl:"/chapter/pdf-preview/61652",authors:[{id:"239293",title:"D.Sc.",name:"Daniel",surname:"Ascencio",slug:"daniel-ascencio",fullName:"Daniel Ascencio"},{id:"246399",title:"Dr.",name:"Rogelio",surname:"Hernández Pando",slug:"rogelio-hernandez-pando",fullName:"Rogelio Hernández Pando"},{id:"246640",title:"Dr.",name:"Miguel Ángel",surname:"Gómez Lim.",slug:"miguel-angel-gomez-lim.",fullName:"Miguel Ángel Gómez Lim."},{id:"246646",title:"Dr.",name:"Sergio",surname:"Ayala",slug:"sergio-ayala",fullName:"Sergio Ayala"},{id:"246691",title:"Dr.",name:"Aaron",surname:"Torres",slug:"aaron-torres",fullName:"Aaron Torres"}],corrections:null},{id:"61187",title:"Clinical Applications of Mesenchymal Stromal Cells (MSCs) in Orthopedic Diseases",doi:"10.5772/intechopen.76868",slug:"clinical-applications-of-mesenchymal-stromal-cells-mscs-in-orthopedic-diseases",totalDownloads:1067,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Mesenchymal stromal cells (MSCs) have the capacity for self-renewal and multi-lineage differentiation, have many advantages over other cells, and are thought to be one of the most promising cell sources for cell-based treatments. In fact, MSCs have already been widely applied in clinics as a treatment for numerous disorders, including orthopedic diseases, such as bone fracture, articular cartilage injury, osteoarthritis (OA), femoral head necrosis, degenerative disc, meniscus injury, osteogenesis imperfecta (OI), and other systemic bone diseases. With the progressions in R&D, the safety and efficacy of MSC-based treatments in orthopedic diseases have been largely recognized, but many challenges still exist. In this chapter, we intend to briefly update the recent progressions and discuss the potential issues in the target areas. Hopefully, our discussion would be helpful not only for the clinicians and the researchers in the specific disciplines but also for the general audiences.",signatures:"Jiazhao Yang, Shiyuan Fang, Lei Xu, Li Li, Kai Xie, Jinsen Lu, Hao\nWang, Xujin Wang and Lixin Kan",downloadPdfUrl:"/chapter/pdf-download/61187",previewPdfUrl:"/chapter/pdf-preview/61187",authors:[{id:"238560",title:"Dr.",name:"Lixin",surname:"Kan",slug:"lixin-kan",fullName:"Lixin Kan"},{id:"245732",title:"Dr.",name:"Yang",surname:"Jiazhao",slug:"yang-jiazhao",fullName:"Yang Jiazhao"},{id:"246322",title:"Dr.",name:"Shiyuan",surname:"Shiyuan",slug:"shiyuan-shiyuan",fullName:"Shiyuan Shiyuan"},{id:"246323",title:"Dr.",name:"Lei",surname:"Xu",slug:"lei-xu",fullName:"Lei Xu"},{id:"246325",title:"Dr.",name:"Li",surname:"Li",slug:"li-li",fullName:"Li Li"},{id:"246326",title:"Dr.",name:"Kai",surname:"Xie",slug:"kai-xie",fullName:"Kai Xie"},{id:"246327",title:"Dr.",name:"Jinsen",surname:"Lu",slug:"jinsen-lu",fullName:"Jinsen Lu"},{id:"246328",title:"Dr.",name:"Hao",surname:"Wang",slug:"hao-wang",fullName:"Hao Wang"},{id:"246329",title:"Dr.",name:"Xujin",surname:"Wang",slug:"xujin-wang",fullName:"Xujin Wang"},{id:"399459",title:"Dr.",name:"Shiyuan",surname:"Fang",slug:"shiyuan-fang",fullName:"Shiyuan Fang"}],corrections:[{id:"65668",title:"Corrigendum to: Clinical Applications of Mesenchymal Stromal Cells (MSCs) in Orthopedic Diseases",doi:null,slug:"corrigendum-to-clinical-applications-of-mesenchymal-stromal-cells-mscs-in-orthopedic-diseases",totalDownloads:null,totalCrossrefCites:null,correctionPdfUrl:null}]},{id:"61292",title:"Human Placenta-Derived Mesenchymal Stromal Cells: A Review from Basic Research to Clinical Applications",doi:"10.5772/intechopen.76718",slug:"human-placenta-derived-mesenchymal-stromal-cells-a-review-from-basic-research-to-clinical-applicatio",totalDownloads:1827,totalCrossrefCites:5,totalDimensionsCites:11,hasAltmetrics:0,abstract:"Placenta-derived mesenchymal stem/stromal cells (PMSC) present several aspects that make them more attractive as cellular therapy than their counterparts from other tissues, such as MSC from bone marrow or adipose tissue in regenerative medicine. Placenta-derived MSC have been used to treat a variety of disorders, such as, cancer, liver and cardiac diseases, ulcers, bone repair, and neurological diseases. Placenta-derived MSC are relatively new types of MSC with specific immunomodulatory properties and whose mechanisms are still unknown. Placenta-derived MSC secrete some soluble factors that seem to be responsible for their therapeutic effects, i.e., they have paracrine effects. On the other hand, Placenta-derived MSC can also serve as cellular vehicles and/or delivery systems for medications due to their migration capacity and their tropism for injury sites. Nanotechnology is an important field, which has undergone rapid development in recent years for the treatment of injured organs. Due to the special characteristics of placenta-derived MSC, the combination of these cells with nanotechnology will be a significant and highly promising field that will provide significant contributions in the regenerative medicine field in the near future.",signatures:"Paz de la Torre, María Jesús Pérez-Lorenzo and Ana I. Flores",downloadPdfUrl:"/chapter/pdf-download/61292",previewPdfUrl:"/chapter/pdf-preview/61292",authors:[{id:"79367",title:"Dr.",name:"Ana Isabel",surname:"Flores",slug:"ana-isabel-flores",fullName:"Ana Isabel Flores"},{id:"248114",title:"Dr.",name:"Paz",surname:"De La Torre",slug:"paz-de-la-torre",fullName:"Paz De La Torre"},{id:"248128",title:"MSc.",name:"Maria Jesus",surname:"Perez-Lorenzo",slug:"maria-jesus-perez-lorenzo",fullName:"Maria Jesus Perez-Lorenzo"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"7870",title:"Muscle Cells",subtitle:"Recent Advances and Future Perspectives",isOpenForSubmission:!1,hash:"64634d90d737661d1e606cac28b79969",slug:"muscle-cells-recent-advances-and-future-perspectives",bookSignature:"Mani T. 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From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"314",title:"Regenerative Medicine and Tissue Engineering",subtitle:"Cells and Biomaterials",isOpenForSubmission:!1,hash:"bb67e80e480c86bb8315458012d65686",slug:"regenerative-medicine-and-tissue-engineering-cells-and-biomaterials",bookSignature:"Daniel Eberli",coverURL:"https://cdn.intechopen.com/books/images_new/314.jpg",editedByType:"Edited by",editors:[{id:"6495",title:"Dr.",name:"Daniel",surname:"Eberli",slug:"daniel-eberli",fullName:"Daniel Eberli"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"57",title:"Physics and Applications of Graphene",subtitle:"Experiments",isOpenForSubmission:!1,hash:"0e6622a71cf4f02f45bfdd5691e1189a",slug:"physics-and-applications-of-graphene-experiments",bookSignature:"Sergey Mikhailov",coverURL:"https://cdn.intechopen.com/books/images_new/57.jpg",editedByType:"Edited by",editors:[{id:"16042",title:"Dr.",name:"Sergey",surname:"Mikhailov",slug:"sergey-mikhailov",fullName:"Sergey Mikhailov"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1373",title:"Ionic Liquids",subtitle:"Applications and Perspectives",isOpenForSubmission:!1,hash:"5e9ae5ae9167cde4b344e499a792c41c",slug:"ionic-liquids-applications-and-perspectives",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/1373.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2270",title:"Fourier Transform",subtitle:"Materials Analysis",isOpenForSubmission:!1,hash:"5e094b066da527193e878e160b4772af",slug:"fourier-transform-materials-analysis",bookSignature:"Salih Mohammed Salih",coverURL:"https://cdn.intechopen.com/books/images_new/2270.jpg",editedByType:"Edited by",editors:[{id:"111691",title:"Dr.Ing.",name:"Salih",surname:"Salih",slug:"salih-salih",fullName:"Salih Salih"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"49872",title:"Telomeres and Genomic Instability from Precancerous Lesions to Advanced Cancer – Understanding Through Ovarian Cancer",doi:"10.5772/62259",slug:"telomeres-and-genomic-instability-from-precancerous-lesions-to-advanced-cancer-understanding-through",body:'Genomic instability is probably one of the first phases in carcinogenesis and would thus facilitate the accumulation of multiple mutations. This instability was first described in connection with the discovery of microsatellite instability with the hereditary non-polyposis colon cancer (HNPCC) or Lynch syndrome for example. In most cancers, there is another form of genomic instability, that is, the chromosomal instability (CIN), which we will describe in this review [1]. At molecular level, this instability could result in chromosome rearrangements (number and structure), duplication or segregation anomalies during mitosis, along with DNA repair system dysfunction [1–4]. The CIN may be explained by the mutator hypothesis in hereditary cancers (germline mutations in DNA repair genes as
Telomere dysfunction has been described to be one of the initial phases in genomic instability. Telomeres are found at the tips of the chromosomes and consist of a large number of hexamer (TTAGGG)n repeats capped with the multiprotein shelterin complex. Their main function is to protect chromosomal ends from fusion and nucleotidic degradation, which ensures chromosomal stability. Telomeres are regularly shortened during cell division due to incomplete replication of telomeric DNA. Excessive shortening (a “telomere crisis”) activates DNA repair at telomeres leading to CIN and finally cell death. In tumors, telomeres are usually shortened, which makes the cell unstable, but the activation of telomerase (telomere elongation complex generally found only in stem, progenitor, and tumor cells and not in normal somatic cells) maintains the telomere length at a certain level, enabling the survival of these cells [2–4]. These unstable cells can then continue to proliferate and this results in cancer. The interaction between telomeres and p53 would thus represent one of the trigger events in carcinogenesis [5]. In physiological terms, telomere shortening represents a real “genotoxic stress” resulting in activation of the DNA damage signaling pathway (and consequently p53 tumor suppressor protein), finally leading to apoptosis or cycle arrest. When p53 is inactivated by mutations, as is the case in ovarian high-grade serous carcinoma, the telomere dysfunction is neither repaired nor signaled, resulting in genomic instability with the accompanying chromosome aberrations, which are a prelude to cancer [2–6].
DNA double-strand breaks can be the result of telomere dysfunction and are one of the most critical DNA alterations at the origin of genomic instability. One of the first response mechanisms aimed at repairing these breaks is activation of the DNA damage checkpoints. These checkpoints represent the transition state between two cell phases that may be inhibited by genotoxic lesions. There is then a slowing or complete halt in the progression from one phase to the next (checkpoint G1/S or G2/M) or during replication (checkpoint intra-S) [7].
The phosphorylation of ATM (a member of the phosphoinositide 3-kinase or PI3 kinase) occurs first. Then ATM phosphorylates Chk2 p53, H2AX, and 53BP1. Chk2 also phosphorylates p53 (Figure 1) [8–12]. Histone H2AX phosphorylated on residue serine 139, also called γH2AX, is a marker for cellular DNA double-strand breaks. Phosphorylation of H2AX results in the condensation of chromatin each side of the break, which makes γH2AX detectable at nuclear level by immunohistochemistry.
Relationship between telomeres and the DNA damage response pathway. DNA double-strand breaks may be the result of telomere dysfunction with activation of the DNA damage checkpoints. The apical kinase ATM is first activated. Then ATM activates the DNA damage mediators, H2AX and 53BP1. ATM also phosphorylates the downstream kinase Chk2, which phosphorylates p53. ATM may directly activate the effector p53. In non-cancerous situation, this pathway leads to checkpoint arrest, cellular senescence, or apoptosis. In cancerous situation, this cascade may activate tumor proliferation to invasive carcinoma. On the left side, you can see the serous carcinogenic sequence from benign fallopian tube (no p53 mutation) to serous tubal intraepithelial carcinoma (the precancerous lesion with p53 signature) and after that ovarian cancer (with also
Strong expression of γH2AX was detected in most precancerous lesions and was considered to represent an antitumor function. Experimental studies have shown that H2AX-deficient mice were at greater risk of immunodeficiency, infertility, and were also more sensitive to ionizing radiation, all of which can be explained by increased chromosomal instability related to reduced capability of the DNA repair systems. When these mice were also p53 deficient (knock-out), there was an increased risk of tumors [13, 14].
As it has been demonstrated that telomere shortening occurs early during carcinogenesis (being found in 89% of preinvasive lesions of the bladder, cervix, colon, and also the esophagus) [5], we investigated genetic instability in precancerous ovarian lesions, which has been described very recently.
This review concerns high-grade serous ovarian cancer (HGSC) characterized by a higher genomic instability (see below) and very frequent
Four hundred and eighty-nine HGSC were recently studied by the Cancer Genome Atlas Research Network [16].
Recent histopathologic and molecular studies enabled to describe a model of tumorogenesis comprising two pathways [15]:
Type I tumors: These are low-grade tumors for which the pathogenesis would consist of a sequence of cystadenomas/adenofibromas, then borderline tumors and finally progression towards cancer. A lesional continuum has indeed been found, that is, molecular mutations that are common to benign, borderline, and invasive lesions (BRAF and KRAS mutations in over 60% of cases, less frequently mutated PTEN (20%–46%) and β-catenin (≈30%). Note also the recent discovery of ARID1A gene mutations in endometriosis and cancers associated with endometriosis (clear cell and endometrioid cancers) [17].
Type II tumors: These are high-grade tumors from the outset. At the molecular level,
True occult intraepithelial cancerous lesions of the tube (serous tubal intraepithelial carcinoma (STIC)) have been reported unusually often in the distal portion of tubes obtained after prophylactic adnexectomy for BRCA mutation, prompting systematic and meticulous examination of these tubes [18–23]. They show epithelial stratification, nuclear atypicalities with an increase in the nucleocytoplasmic ratio, loss of nuclear polarity, nuclear pleiomorphism, and loss of ciliated cells. Immunohistochemical analysis may reveal intense and diffuse expression of
In other words, high-grade ovarian serous carcinoma could originate in the fallopian tube, and all these findings encouraged us to study STIC lesions and genomic instability.
We started by assessing the telomere length in 12 STICs, 36 non-cancerous controls, and 43 high-grade serous cancers [24, 25]. Laser microdissection of paraffin-embedded samples was used in all cases. A DNA extraction was followed by purification step. Telomere length was measured by real-time quantitative polymerase chain reaction (PCR) according to Cawthon’s method [26].
STICs had the shortest telomeres (p=0.0008). Telomeres of invasive cancer were shorter than those in benign controls but longer than telomeres found in STICs. A significant correlation was also found between overexpression of p53 and H2AX proteins and shortened telomeres in STICs (p<10−7) [24]. Kuhn
We also studied these STICs by array comparative genomic hybridization (aCGH) using oligonucleotide microarrays (Agilent 180 K) [24].
The size of rearrangements in STICs was high, with an average of 2363.37 Kb (488–8161).
We found common gains at chromosomes 19q (6/12, 50%), 16p (5/12, 41.6%), 12q (5/12, 41.6%), 10q (5/12, 41.6%), 11p (4/12, 33.3%), 4p (3/12, 25%), and 8q (3/12, 25%), and common losses at chromosomes 3q (6/12, 50%), 2q (5/12, 41.6%), 11q (4/12, 33.3%), 6p (4/12, 33.3%), 22q (4/12, 33.3%), 18q (3/12, 25%), 19p (3/12, 25%), 20p (3/12, 25%), and 2 p (2/12, 16.6%) [24]. These early rearrangements could be key steps in these first phases of carcinogenesis, and the corresponding candidate genes could be involved directly in the tumor triggering process, meaning that they could represent diagnostic and/or treatment targets. More studies are required.
Finally, in another study, we investigated the level of DDR activation in STICs by immunohistochemistry (pATM, pChk2, γH2AX, 53BP1, and TRF2) [28]. We constructed a tissue microarray, including 21 benign fallopian tubes, 21 STICs, and 30 HGSCs. We demonstrated that the expression of all DDR proteins increased from benign fallopian tubes to STICs. Analysis of staining variance within cases showed that 53BP1, γH2AX, pATM, pCHK2, and TRF2 expressions were significantly higher in STICs than in HGSC [28].
Taken together, all our results have shown evidence of genomic instability in the precancerous lesions known as STICs. Of note among the frequent chromosomal breakpoints in STICs, more than half occurred at terminal bands, which is characteristic for a telomere crisis with the occurrence of telomere fusions, leading to chromosomal aberrations.
It could also be interesting to study human telomerase reverse transcriptase (hTERT) expression, which is a determinant for telomerase activity, and also the telomere architecture proteins (shelterin complex proteins TRF1, TRF2, and POT1) in STICs and HGSC [29–33]. TRF1 and TRF2 proteins are involved in negative regulation of telomere lengthening and interact with telomerase [29, 30]. POT1 appears to play a dual antagonist role, depending on cell conditions, acting as positive or negative regulator of telomere length depending on telomerase [6, 34]. In our study [28], the level of expression of TRF2 was increased in STICs in comparison with HGSC (p=0.012). It has been shown that TRF2 may shorten telomeres without telomerase inactivation [12]. TRF2 is also phosphorylated by ATM to enable DNA damage repair in response to DNA damage [12].
Telomerase would probably be activated after telomere shortening at the invasive stage and would thus counteract further telomere shortening: stabilization of telomere length at this stage would moreover represent an advantage in terms of tumor proliferation and escaping apoptosis [3].
Wang
Other authors demonstrated that telomerase activity was higher in ovarian carcinoma than in borderline tumors (considered as premalignant tumors) and normal ovary [36–38]. This was confirmed in cell cultures [39]. However, telomerase activity in STICs has not yet been studied.
Telomere shortening has been proven to be one of the potential precursors of ovarian cancer indicative of genomic instability. This could lead to significant preventive strategies such as prophylactic salpingectomy in patients with a genetic risk of ovarian cancer in order to avoid the malignant transformation of benign fallopian tube into STIC [40].
Today’s global population is estimated to be over 7.9 billion people, which is expected to reach 9.9 billion in 2050, 34% higher than it is now [1]. Developing countries will account for nearly all of this overpopulation. To feed this growing population, agricultural lands must be used considerably more effectively, and production should be boosted by 70% compared to today’s values [2]. Besides, agricultural production areas are unfortunately facing major ecological challenges, owing to human misapplications, natural calamities, as well as the impact of global climate change [3]. As a result of these factors, today the condition of our current lands is deteriorating leaving us with no choice but to grow nutrient-rich, chemical-free agricultural produce for human and animal use while using far less water and arable land than in the past. This is why a focus on both quality and quantity should be placed on food production without depleting natural resources. Developing and disseminating improved agricultural methods and technologies are equally critical.
Since cultivation areas are dwindling year after year, fertilizer mineral is a world market item that is vital to produce a higher plant yield per unit area and attain food security. It must be available in adequate quantities and in the proper balance to close the gap between nutrient supply from soil and organic sources and nutrient demand for optimal crop development [4]. Not just that, fertilizer is critical for the nation’s economy to grow, as agriculture is the primary source of employment. By 2025, it will ensure food security for more than 8 billion people around the globe [5]. The increase in the use of chemical fertilizers by approximately 5 million tons in 10 years is a situation that should be considered while the agricultural areas are decreasing. However, it is more necessary to keep the soil’s plant nutritional balance by considering climate, soil, and plant characteristics rather than the amount of chemical fertilizers utilized, and fertilizing based on soil analysis is critical.
Fertilizer is recognized as one of the most valuable agricultural production inputs, and synthetic fertilizers are becoming increasingly popular around the world. The global fertilizer market was valued at $155.8 billion in 2019, with a compound annual growth rate (CAGR) of 3.8% predicted for the forecast period (2019–2024) [6]. Fertilizer consumption climbed from 10,777,779 million tons in 2015 to 14,495,815 million tons in 2020, a record high. The total global demand for fertilizers (N + P + K) was estimated at 198.2 million metric tons (mmt) in 2020/2021, according to the International Fertilizer Association (IFA). This was nearly 10 mmt, or 5.2% higher than in 2019–2020 and was the highest rise since the 2010–2011 fiscal year. Nitrogen experienced a 4.1% increase in demand to 110 mmt. Phosphorus demand increased by 7.0% (3.3 Mt), reaching 49.6 Mt., while demand for potash rose by 6.2% (2.2 Mt) to 38.5 Mt. [7]. In the last 50 years, the amount of chemical fertilizer used throughout the world has increased dramatically (Figure 1) [8].
Global usage of chemical fertilizer since 1970 [
Chemical fertilizers have also become more popular in Turkey in recent years, where the cultivation areas are decreasing every year, the need for fertilization is increasing, since more plant production per unit area is required. According to TUIK (Turkish Statistical Institute) 2021 statistics, both the use of fertilizers and nitrogen fertilizers has increased in agricultural production in Turkey in the last 10 years. TUIK statistics showed that annual fertilizer use in Turkey increased from 9,074,308 tons to 14,495,815 tons between 2010 and 2020, and the use of nitrogenous fertilizers increased from 5,995,500 tons to 9,774,691 tons within these values. The amount of fertilizer per unit production area is 107 kg/ha. The use of chemical fertilizers in agricultural inputs accounts for a share of 15–20% [9].
Advances in fertilization and agricultural applications have led to a significant increase in crop productivity in many regions, including Turkey. The most important chemical fertilizers applied to obtain more efficiency in plant production are those containing nitrogen, phosphorus, and potassium. Nitrogen fertilizers (N), however, are the most widely used chemical fertilizers in the world, as well as in Turkey, and play a unique role in plant production. Potassium fertilizers (K2O) are the second most consumed after nitrogen, followed by phosphorus fertilizers (P2O5) [8].
It has been determined that 87% of agricultural lands in Turkey have poor organic matter content [10]. Therefore, agricultural production is supported by fertilization, and nitrogen fertilizers constitute an important part of the total fertilizer applied. According to TUIK data, nitrogenous fertilizer usage rates as a percentage of total fertilizer use have shifted between 65 and 69% in the last 10 years [9]. Fertilizer use benefits plants in a variety of ways, including being a less expensive source of nutrients, having significant nutrient content and solubility, making it easily available to plants, and requiring less fertilizer, hence making it more suited than organic fertilizer [11]. Despite these advantages, mineral fertilizer has a number of negative environmental consequences as a result of rising consumption and decreased nutrient utilization efficiency. As a result, in intensive agricultural production systems, integrating intense cultivation with high nutrient utilization efficiency is a key difficulty.
Though conscious fertilization is desirable, the use of improper fertilizers can be extremely harmful, posing severe problems for current and future generations [12]. Sometimes, unfortunately, a wrong perception occurs among the producers of chemical fertilization. It is thought that more efficiency can be obtained by using more chemical fertilizers. Contrary to popular belief, the “LAW OF DECREASING PRODUCTION” is valid in fertilization. That is, the benefit derived from fertilization rises up to a point, after which continuing to apply fertilizer causes harm rather than a benefit.
The unintended and excessive use of chemical fertilizers to boost yields, as well as rising reliance on them, has a negative impact on the agricultural production system’s sustainability as well as financial losses in many countries today [13]. Certain factors, such as changes in fertilizer type, variations in application times, the producer’s lack of understanding in this area, and improper fertilizer applications, in particular, have been found to have quite substantial environmental consequences and threatening effects on the health and life of living creatures [14]. The inefficient and not demand-oriented fertilization applications in agricultural production can lead to soil acidity and soil crust, low organic matter and humus content, heavy metal accumulation, decrease in pH values, soil salinity, plant nutritional imbalances, limited plant growth, erosion, a decline in microbial activity and efficacy and emission of gasses containing substances that damage the atmosphere and the ozone layer, and eventually the greenhouse effect [15].
The issues at the forefront of the detrimental environmental effects of chemical fertilizers are highlighted here.
Excessive soil acidity induced by fertilizers is a major cause of soil degradation across the world. Fertilizers, especially nitrogen, acidify soil when applied in excess. This scenario has negative consequences, such as the crops’ incapacity to absorb phosphate, the proliferation of hazardous ion concentrations in the soil, hindrance of crop development, and suppression of microorganism activity [16]. If ammonium sulfate fertilizer is given to acidic soil, for example, the acidity level will become even higher. One-way ammonium sulfate fertilization of tea, according to research conducted in the Rize province of Turkey, considerably increased the acidity of low-pH soils. Currently, 85% of the land has fallen below pH 4, which is deemed critical. Likewise, in Nevsehir province, the pH of the soil has dropped to 2 as a result of nitrogen fertilization of potatoes grown in 100-fold increasing acidity over the last 25 years [17].
Hao et al. [18], carried out a field experiment to measure soil acidification rates in response to varied fertilizer sources and N rates, including control, optimal urea, conventional urea, optimized NH4Cl, and conventional NH4Cl plots, nitrogen addition resulted in average H+ production of 4.0, 8.7, 11.4, 29.7, and 52.6 keq ha−1 yr.−1, respectively. This was followed by a 1–10% decrease in soil base saturation and a 0.1–0.7 unit decrease in soil pH in the topsoil (0–20 cm). In a greenhouse study conducted to evaluate the effect of conventional nitrogen fertilizer on soil salinity and acidity, a significant rise in both soil acidity and salinity was witnessed as N input increased after one season, with pH decrease ranging from 0.45 to 1.06 units [19]. Moreover, after 21 years of application, chemical N fertilizer dropped the soil pH from 6.20 to 5.77, a 0.02 pH unit drop per year [20]. In another study, an evaluation of the impact of long-term fertilizing techniques on soil samples revealed a fall in soil pH from 8.4 to 7.5 [21]. Because nutrients are less available to plants in acidic soil, serious plant nutritional deficiencies are prevalent, resulting in overall crop reduction.
Heavy metal deposition in soils is mostly caused by the manufacture and consumption of industrial products, although fertilizers and pesticides used in agriculture also contribute significantly. Arsenic (As), copper (Cu), nickel (Ni), cadmium (Cd), and uranium (Ur), among other heavy metals, can build up in the soil following repeated chemical fertilizer applications, particularly phosphorus (P) fertilizers and their source material [22, 23, 24]. These toxic heavy metals not only pollute the environment, but they may also cause soil degradation, plant development retardation, and perhaps impair human health through food chain contamination harming the central nervous system, circulatory system, excretory system, and cardiovascular system, as well as cause bone damage, endocrine disruption, and possibly cancer [25].
Phosphorus (P) fertilizer is widely utilized in agriculture due to its vital function in crop growth and production [26]. However, P fertilizer has been recognized as the predominant cause of HMs pollution in soil when compared to potassium (K) and nitrogen (N) fertilizers [27]. According to a 10-year field trial, P fertilization aided Zn, Pb, Cd, and As buildup in the topsoil. With increasing P application, the threshold cancer risk (TCR) associated with As and Cd increased [28]. Likewise, another experiment concluded that frequent application of P fertilizer and the extended residence period of HMs may generate a large accumulation of HMs in soils [29].
Heavy metals are concentrated in agricultural soil as a result of improper application of commercial fertilizers, manure, sewage, or sewage sludge [30]. The results of the study conducted by Huang and Jin [31] suggested that the long-term usage of exaggerated synthetic fertilizers and organic manures contributed to the heavy metals (HMs) accumulation in the soils. Research carried out by Atafar et al. [32], confirmed that the fertilizer use enhanced the amounts of Cd, Pb, and As in cultivated soils. Before fertilization, the Cd, As, and Pb concentrations in the studied location were 1.15–1.55, 1.58–11.55, and 1.6–6.05 mg/kg, respectively; after harvesting, values were 1.4–1.73, 26.4 5.89, and 2.75–12.85 mg/kg soil for Cd, As, and Pb, respectively. The findings of another study concluded that chemical fertilizer usage increased the availability of Cu, Ni, Pb, and Zn as well as the buildup of Cd, Cu, and Zn in the greenhouse soil [33].
Salts are a common component of chemical fertilizers and are considered destructive to agriculture because they harm soil and plants. Increases in the salinity of the soil can be seen by natural or artificial means. Artificially induced salinity is the result of the accumulation of fertilizers used in large quantities over long periods of time in areas where intensive farming is practiced, making the soils unsuitable for production [22, 34, 35]. Following one season of conventional nitrogen fertilizer, electrolytic conductivity increased from 0.24 to 0.68 mS cm−1 [19]. Long-term intensive farming raised soil electrical conductivity (ECe), which rose from “low salinity” (1.5 dS m−1 0.49) to “highly saline” (6.6 dS dS m−1 1.35) levels [21].
Soil salinity is a major global issue that has a negative impact on agricultural output. Salinization of agricultural land diminishes economic advantages greatly, as demonstrated by Welle and Mauter [36] in California, where salinization lowered overall agricultural income by 7.9%.
Inorganic fertilizers used recklessly can cause nutritional imbalances in the soil, thus limiting the intake of other essential nutrients. If the common NPK type is frequently used, secondary and micronutrient deficiencies occur in the soil and crop. Excess nitrogen and phosphate fertilizers, for instance, enable the plant to absorb more potassium than it requires. In acidic soils, lime and lime-containing fertilizers lead to the retention of micro plant nutrients, such as P, B, Fe, and Zn in the soil. Over-applied phosphorus fertilizers also prevent the uptake of nutrients, such as Ca, Zn, and Fe, and reduce their efficacy [22, 37].
Soil compaction is a key component of the land degradation syndrome and a serious issue for modern agriculture, negatively impacting soil resources [38]. Overuse of fertilizers for extended periods of time and intensive cropping are two of the main causes of compaction. Chemical fertilizers damage soil particles, resulting in compacted soil with poor drainage and air circulation [39]. Reduced soil aeration has an impact on soil biodiversity. Microbial biomass may be diminished as a result of severe soil compaction. Soil compaction may not affect the amount of macrofauna, such as earthworms, but it does affect the distribution of macrofauna, which is important for soil structure.
Soil compaction leads to high soil strength and bulk density, poor drainage, poor aeration, limited root growth, erosion, runoff, and soil deterioration, hence resulting in low permeability, hydraulic conductivity, and groundwater recharge [40, 41]. High soil compaction stifles root growth, reducing the plant’s ability to absorb nutrients and water. Compaction, according to reports, reduces root growth and yield by more than 80% [42]. As the soil bulk density increases, nitrification drops by 50%, and plants use less N, P, and Zn from the soil [43]. The findings of the research conducted by Massah and Azadegan [44] suggested that in non-compacted and severely compacted soils, bulk density increased from 1.34 to 1.80 Mg.m−3, and penetration resistance increased from 0.89 to 3.54 MPa, respectively. Soil compaction reduced permeability by 81.4%, accessible water by 34%, and yields by 40%.
In agricultural production, the unintentional, excessive, or random application of chemical fertilizers and pesticides degrades the chemical, biological, and physical structure of the soil, resulting in a rise in pathogen and pest populations [45, 46]. Moreover, with intensive and unconscious chemical fertilizer applications, the amount of organic matter in the soil decreases, which adversely affects the microorganism activities and causes the structure of the soil to deteriorate. If the same fertilization errors are repeated, soil structures will deteriorate with each passing year, plant growth will slow as fertilizer doses are increased, and the overall amount of product obtained will decrease. Some of the fertilizers will not be able to hold on to the soil and will be removed with the water. The conversion of nutrients into forms that plants can benefit from will be reduced.
Soil microbial activity is a crucial component of soil health, and soil organisms serve as a mechanism for nutrient recovery, as well as provide a variety of other environmental functions. Chemical fertilizer misuse can have a detrimental and lethal effect on soil quality and microbial community structure, including earthworms, and other soil inhabitants. Prolonged consumption of chemical fertilizers can cause a significant drop in soil pH, which has been associated with a decrease in bacterial diversity and major changes in bacterial community composition [47]. Nitrogen usage in agriculture has a deleterious influence on the nitrogen cycle and the activities of related bacterial communities, including nitrogen-fixing microorganisms such as Rhizobium sp. [48]. Besides, excess nitrogen fertilizers limit the activities of nitrifying bacteria [49].
It is critical to emphasize the importance of understanding how to apply chemical fertilizers properly. Chemical fertilizers, as part of their larger threat to the environment, animals, and human health, eventually leak into our water bodies, such as ponds, streams, and groundwater, contaminating water supplies, exposing humans and animals to a variety of short- and long-term hazardous chemical effects on their health and bodies. In ideal conditions, it is estimated that roughly 2–10% of fertilizers interfere with surface and groundwater [50]. The accumulation of nitrates in the water emerges as a result of the use of N fertilizers in the agricultural field, which is increasing day by day. Even under ideal conditions, only 50% of the nitrogen fertilizer given to the soil can be taken up by plants; 2–20% evaporates, 15–25% combines with organic compounds in the clay soil, and 2–10% is discharged into streams, rivers, and streams with surface runoff [50, 51]. Nitrate, a frequent contaminant of surface and groundwater, can cause serious health concerns, including inflammation of the colon, stomach, and urine systems. Furthermore, these compounds have been reported as carcinogens that can have a harmful impact on human health. They also have the potential to induce disorders in infants, such as methemoglobinemia, a condition in which the blood carrying capacity is limited due to a decrease in hemoglobin.
Though the rise in agricultural productivity alleviated poverty, it also posed a threat to the ecosystem due to its negative consequences. Rising levels of synthetic fertilizer application for agricultural production, for instance, increase greenhouse gas emissions, eroding the protective ozone layer, and exposing humans to harmful ultraviolet radiation [52]. Above all, agriculture is responsible for a major fraction of the greenhouse gas (GHG) emissions that are driving climate change, accounting for 17% directly from agriculture activities and another 7–14% through land-use changes.
During the production of nitrogenous fertilizer, greenhouse gases, such as CO2, CH4, and N2O are released. Moreover, nitrous oxide emissions from soils, fertilizers, manure, and urine from grazing animals, as well as methane generation by ruminant animals and paddy rice agriculture, are the most significant direct agricultural GHG emissions. Both of these gases have a far larger potential for global warming than carbon dioxide.
Agriculture is the primary source of anthropogenic N2O emissions, accounting for 60% of total emissions. It has a 310-fold greater global warming potential than carbon dioxide. Excess nitrogen fertilizer application results in nitrogen oxide emissions (NO, N2O, NO2), which cause serious air pollution [51]. The primary issue with nitrous oxide emissions is the impact of global warming and the function of nitrous oxides in ozone degradation, encouraging the decomposition of the ozone layer [53] and resulting in atmospheric “holes,” exposing humans and animals to excessive UV radiation [54]. Water vapor, hydrogen sulfide, and chloro-fluoro hydrocarbons are among the other gases that contribute to ozone depletion [55].
After being volatilized or released from fertilized fields, ammonia is deposited in the atmosphere and oxidized to generate nitric and sulfuric acids, resulting in acid rain. Acid rain has the potential to harm flora, buildings, and species that live in lakes and reservoirs [56]. Methane emissions from transplanted paddy fields are also a major concern, as methane is a powerful greenhouse gas whose concentration is doubled when ammonium-based fertilizers are used. These gases all contribute to global warming and climate change [57].
Climate change is gaining traction, resulting in major global temperature spikes, as well as the prevalence of additional abiotic stressors that are reducing crop output. Significant production losses in major grain crops have been attributed to climate change, resulting in 3.8% yield reductions for maize and 5.5% for the wheat [58, 59].
Fertilization, which is one of the most essential inputs in agricultural operations, increases productivity on the one hand, but its overuse might have negative consequences on the other. Excessive usage of agricultural chemicals jeopardizes the long-term viability of agriculture. Today, the fast expansion in agricultural productivity has begun to slow down [45, 56]. Clean food production becomes inevitable with a healthy and reliable agriculture system that does not require chemicals.
Given that chemical fertilization cannot be completely eliminated in agricultural applications, in this scenario, sustainability initiatives and the usage of ecologically sound technologies can help achieve the goal of enhancing healthier crop productivity whilst eliminating unnecessary input and thereby mitigating harsh weather conditions, as well as improving soil health by sequestering carbon and retaining organic material and mineral nutrients in the soil [60]. Hence, it is vital to use alternatives, such as Plant-Growth-Promoting Rhizobacteria (PGPR), to support sustainable agricultural productivity and everlasting soil fertility and to build production strategies that will aid in the proliferation of beneficial soil microorganisms activities.
The rhizosphere is a well-defined ecological niche that consists of the volume of soil surrounding plant roots and is home to a wide range of microbial species [61, 62]. As a result of phytomicrobiome research, certain plant-microbe interactions that directly aid in plant nutrition are beginning to emerge [63]. Microbes have the power to positively influence plant growth and combat the majority of modern agriculture’s challenges, making them a promising alternative for agricultural sustainability. The rhizomicrobiome is indispensable for agriculture because of the extensive diversity of root exudates and plant cell debris that attract diverse and unique patterns of microbial colonization. Fertilizer requirements are often lower in soils with dynamic microbial ecologies and rich organic matter than in traditionally treated soils [64].
Despite the fact that the rhizosphere is home to a diverse range of microbes, including bacteria, fungi, algae, protozoa, and actinomycetes, bacterial colonies are predominant [65, 66]. The bacterial community in the soil, in particular, has the potential to proliferate quickly and use a wide variety of nutrient sources. A group of natural soil bacterial flora that resides in the rhizosphere and grows in, on, or around plant roots [67] and has a beneficial effect on the plant’s overall health is referred to as PGPR [68]. PGPR is a nonpathogenic, beneficial bacterium that promotes plant growth by modifying hormone levels and nutritional requirements, as well as reducing stress-related damage [69]. Nutrient absorption is thought to be increased as a result of the increased root surface area mediated by PGPR. Besides, they mineralize organic contaminants and are employed in polluted soil bioremediation [70]. When compared to other microorganisms, PGPR has unique characteristics, such as the ability to synthesize growth regulators, nitrogen fixation, phosphorus solubilization, siderophore generation, nutrients, and mineral solubilization, demonstrating their exceptional tendency in stimulating plant growth [71]. They are also environmentally friendly and ensure that nutrients from natural sources are available at all times. In addition to stimulating plant growth through their active mechanisms, the bacterial colonies in the rhizosphere have a considerable influence on suppressing phytopathogenic microorganisms. Beneficial rhizobacteria can emit antibiotics and other chemicals that are effective at inhibiting pathogens [72].
The fundamental impacts that rhizosphere bacteria have on plants have evolved into an important mechanism for protecting plant health in an environmentally sustainable manner [73]. They participate in a variety of biotic activities in the soil ecosystem to keep it active and productive for farming systems [74]. Furthermore, in recent times, PGPR has garnered much attention for its potential to substitute agrochemicals for plant growth and yield through multiple processes, including decomposition of organic matter, recycling of essential elements, soil structure formation, production of numerous plant growth regulators, degrading organic pollutants, stimulation of root growth, and solubilization of mineral nutrients, which are important for soil health [75]. It is cost-effective and environmentally beneficial to replace chemical fertilizers with PGPR, as well as to identify the most effective soil and crop management approaches in an attempt to develop more sustainable farming and soil conservation fertility [76]. The employment of phytomicrobiome representatives as a long-term disease prevention and nutrient supplement method in farming production might help to reduce the negative impacts of pesticide usage [77]. The inoculated plant’s biocontrol and induction of disease resistance, biological N2 fixation, phosphate solubilization, and/or phytohormone synthesis are all potential explanations for PGPR’s growth-promoting actions [78].
PGPR has both direct and indirect modes of action as a biofertilizer and a biopesticide.
One of the most prevalent ways for increasing agricultural production is to improve soil fertility. PGPR promotes soil fertilization through the biofixation and biosolubilization processes (Figure 2).
PGPR’s mechanism of action [
Nitrogen (N) is found in all forms of life and is one of the most significant mineral nutrients for plant growth as it is a crucial component for various physiological activities in plants, including photosynthesis, nucleic acids, and protein synthesis [80]. Unfortunately, due to the low degree of reactivity, no plant species are capable of directly converting atmospheric dinitrogen into ammonia and using it for growth, hence making the plants dependent on biological nitrogen fixation (BNF). Nitrogen fertilizer, as being the most effective approach to nitrogen supplementation, has been an integral part of modern crop production and agricultural systems; yet, their continued and undesirable use is contaminating the climate. Though carbon dioxide (CO2) is widely regarded as the primary cause of climate change, nitrous oxide (N2O), which has a 265-fold higher heat-trapping efficiency than CO2 [81], is indeed a significant contribution. PGPR in this regard is a potential alternative to minimize the fertilizer requirements to a certain degree as the majority of the plant microbial community can either directly fix atmospheric nitrogen through legume-rhizobium interaction or indirectly by helping nitrogen fixers via their secretion [82].
Worldwide, total N fixation is estimated to be ∼175Tg, with symbiotic nitrogen fixation in legumes accounting for ∼ 80 Tg by fixing 20–200 kg N year-1, while the remaining nearly half (∼88 Tg) is industrially fixed during the production of N fertilizers [83]. The most prominent symbiotic nitrogen fixer is Rhizobium [84], whereas Azospirillum, Acetobacterdiazotrophicus, Azotobacter, Herbaspirillum, Cyanobacteria, Bacillus, Paenibacillus, Gluconacetobacter, and Azoarcus, etc., represent the free-living N fixers [85].
Symbiotic nitrogen fixation: A mutualistic association between a microorganism and a plant is known as symbiotic nitrogen-fixing. The N-fixing symbiosis between rhizobia and legumes is the most well-studied and utilized beneficial plant-bacteria interaction. In this interaction, legumes supply rhizobia with reduced carbon and a protected, anaerobic environment that is necessary for nitrogenase activity, while rhizobia feed legumes with biologically accessible nitrogen. The bacteria enter the root first, causing the growth of nodulation, which converts atmospheric nitrogen into usable forms (primarily NH3) [86]. Rhizobia can fix up to 200 kg of nitrogen ha − 1 by establishing symbiotic relationships with more than 70% of leguminous plants, thus making it available to plants.
Free-living nitrogen-fixing: Several nitrogen-fixing microorganisms do not interact in a symbiotic manner. These microorganisms are free-living and rely on plant leftovers or their own photosynthesis to exist. Although free-living nitrogen fixers do not enter the plant’s tissues, a tight interaction is developed where these bacteria reside close enough to the root that the atmospheric nitrogen fixed by the bacteria is taken up by the plant, resulting in greater nitrogen absorption. Besides, other bacteria that do not fix nitrogen have been demonstrated to boost nitrogen uptake in plants, resulting in increased nitrogen use efficiency [87], most likely due to increased root development, which allows plants to reach more soil [63]. Evidence of PGPR involvement in the plant N budget has been identified for various plants, particularly sugarcane [88].
Rhizobial N-fixation is an integrated approach for disease control, growth stimulation, as well as providing and maintaining the nitrogen level in agricultural soils around the world, thus minimizing the need for extensive N-fertilizer application and limiting the soil and environmental challenges associated with it.
Phosphorus (P) is the most significant vital element in plant nutrition (N), alongside nitrogen [89]. It is involved in a number of major metabolic activities in plants, including macromolecular biosynthesis, photosynthesis, respiration, energy transfer, and signal transduction [90]. Although most soils hold a significant amount of phosphorus, which builds over time as a consequence of fertilizer treatments, plants have access to only a small portion of it. Despite the fact that P is abundant in both organic and inorganic forms in the soil, only 0.1% of it is available to plants because 95–99% of phosphate is either insoluble, immobilized, or precipitated [91]. Plants can absorb mono and dibasic phosphate on their own, but organic and insoluble phosphate must be mineralized or solubilized by microorganisms [92]. Phosphate anions are highly reactive and, depending on the soil quality, can be trapped by precipitation with cations including Mg2+, Ca2+, Al3+, and Fe3+. Plants cannot absorb phosphorus in these forms because it is highly insoluble. As a result, plants only get a small percentage of the total.
When deficient, phosphorus-based fertilizers are typically used to replenish soil P, which is readily available to plants. Supplementing P with commercial fertilizers, however, is not an ideal option due to their high cost and sometimes inaccessibility to plants since they are easily lost from the soil and subsequently mix with local streams, contaminating both terrestrial and aquatic environments [93]. Therefore, phosphorus solubilization, in addition to nitrogen fixation, is also vital biologically. Phosphate solubilization is among the most profound consequences of PGPR on plant nutrition. Persistent plant growth, PGPR, plays a major role in solubilizing phosphorus [94]. The potential of various bacterial species to solubilize insoluble inorganic phosphate compounds such as dicalcium phosphate, tricalcium phosphate, rock phosphate, and hydroxyapatite has been documented by many researchers. Phosphate can be dissolved in insoluble forms by a variety of PGPR, including Pseudomonas, Bacillus, and Rhizobium. PGPR solubilizes P by employing a number of mechanisms, including the synthesis of organic acids and extracellular enzymes, to make use of inaccessible forms of P, hence assisting in the availability of P for plant absorption. Miller et al. [95] pointed out two processes—acidification of the external medium via the release of low molecular weight organic acids (such as gluconic acid) that chelate phosphate-bound cations and the formation of phosphatases/phytases that hydrolyze organic forms of phosphate compounds. Phosphorus solubilizing bacteria (PSB) has been shown to lower the recommended P dose by approximately 25% [96] and is even more efficacious when combined with other PGPRs or mycorrhizal fungi, reducing the P supplementation to 50%. As a result, the risk of P runoff and eutrophication is mitigated [97].
Potassium (K) deficit has become a severe crop production bottleneck. Plants with insufficient potassium have poor root development, low seed production, a slow growth rate, and a decreased yield. Soluble potassium concentrations in soil are typically low; over 90% of the potassium in the soil is in the form of insoluble rocks and silicate minerals [98]. Several microbes, particularly fungal and bacterial genera, have close connections with plants and can release potassium in accessible form from potassium-bearing minerals in soils through the synthesis and secretion of organic acids [99, 100, 101]. Setiawati and Mutmainnah [101] synthesize organic acids produced by soil microorganisms, such as acetate, ferulic acid, oxalate, coumaric acid, and citrate, which significantly increase mineral dissolution rates and proton production by acidifying the soil rhizosphere and resulting in mineral K solubilization. As a result, using potassium-solubilizing PGPR as a biofertilizer in agricultural production can reduce agrochemical use while also encouraging environmentally friendly crop production.
Iron (Fe) is a major bulk mineral abundantly available on Earth, yet it is inaccessible in the soil for plants, owing to the fact that Fe3+ (ferric ion), the most common form of Fe found in nature, is hardly soluble [102]. PGPRs are the right fit to address this issue as they produce siderophores, which are tiny organic compounds that increase Fe absorption capability when it is scarce. Since PGPR can form siderophores, they are a valuable asset in supplying the plant with the necessary iron. Siderophores released by PGPRs boost plant growth and development via facilitating access to Fe in the soil surrounding the roots [103]. Plant growth can be stimulated directly by siderophore-producing bacteria, which improves plant Fe intake, or indirectly by suppressing the activities of plant pathogens in the rhizosphere, which limits their Fe availability [104]. Pathogen suppression is induced by the synthesis of siderophores, which decrease pathogen survival by chelating available Fe and therefore restricting pathogen survival [105]. In the presence of other metals, such as nickel and cadmium, a robust siderophore, such as the ferric-siderophore complex, is crucial for Fe uptake by plants [106]. Siderophores alleviate stress on the plants caused by potentially hazardous metals, such as Al, Cd, Cu, Pb, and Zn, found in polluted soil via forming stable compounds with them [107]. This phenomenon is beneficial for reducing plant stress induced by potentially harmful metals found in contaminated soils. Furthermore, siderophore-expressing rhizobacteria could be a potential alternative to chemical fertilizers by concurrently addressing salt-stress effects and Fe limitation in saline soils.
One of the many advantages of rhizobacteria in encouraging plant growth and controlling plant diseases is their ability to synthesize polysaccharides. Multifunctional polysaccharides, for instance, structural polysaccharides, intracellular polysaccharides, and extracellular polysaccharides, are synthesized by specific bacteria. Exopolysaccharide production is critical for biofilm development, and root colonization can influence microbial interactions with root appendages. The colonization of plant roots by EPS-producing bacteria aids in the separation of free and insoluble phosphorus in soils, circulating critical nutrients to the plant for appropriate growth and development, as well as protecting it against disease attacks. EPS-producing bacteria have a variety of roles in plant-microbe interactions, including protection against desiccation, stress [108], adherence to surfaces, plant invasion, and plant defense response [109]. Plant exopolysaccharides produced by plant-growth-enhancing rhizobacteria are critical in stimulating plant growth because they act as an active signal molecule during beneficial interactions and generate a defense response during the infection phase [110]. Some plant-growth-promoting rhizobacteria that produce exopolysaccharides can also bind cations, including Na+, implying that they may play a role in limiting the amount of Na + available for plant uptake and thereby reducing salt stress [111].
Phytohormones, commonly known as plant growth regulators, are organic chemicals that, at low levels (less than 1 mM), promote, inhibit, or modify plant growth and development [112]. Phytohormones are categorized based on where they act. Botanists recognize five main kinds of phytohormones: Auxins, Gibberellins, Ethylene, Cytokinins, Ethylene, and Abscisic acid.
Phytohormones stimulate root cell proliferation by overproducing lateral roots and root hairs, resulting in increased nutrition and water intake [113]. This is crucial for regulating nutrient uptake depending on soil composition and environmental circumstances. Slower primary root development and a spike in the proportion and length of lateral roots and root hairs are the most common effects.
Phytohormones play an important role in regulating developmental processes and signaling networks that are involved in plant adaptation to a variety of biotic and abiotic stressors [114]. Abiotic stressors, however, disrupt plant growth by altering endogenous levels of phytohormones [115]. Surprisingly, some bacteria, such as PGPR, may stimulate plants to produce phytohormones.
A diverse spectrum of rhizospheric microorganisms is capable of producing growth hormones that can promote cell proliferation in the root architecture by inducing an increase in nutrition and water intake by encouraging root hair growth, thus regulating overall plant growth and development, as well as activating pathogen defensive responses [116]. Important biological rhizobacteria can adjust to their surroundings and develop stress tolerance by repairing plant roots. The production of growth metabolites by PGPRs may help provide water stress resistance in host root colonization, resulting in higher optimal crop output.
Auxin is a critical molecule that regulates most plant functions, either directly or indirectly, and indole-3-acetic acid (IAA) is the most abundant and physiologically potent phytohormone that regulates gene expression by upregulating and downregulating it [116, 117]. More than 80% of rhizospheric bacteria have been known to be capable of synthesizing and releasing auxins. IAA produced by PGPR regulates a wide range of processes in plant development and growth, including cell division, differentiation, organogenesis, tropic responses, primary root elongation, and the formation of lateral roots [118]. As a result of the increased root surface area and length mediated by bacterial IAA, plants have better access to soil nutrients. Under salinity stress circumstances, the secretion of IAA by PGPR may have a key function in managing and regulating IAA concentrations in the root system, resulting in improved plant salinity stress responses [119]. Besides, microbe-induced IAA can boost root and shoot biomass output in water-stressed situations [120].
Gibberellins (GA) are another type of phytohormone produced by rhizobacteria. Different activities in higher plants, such as seed germination, root and leaf meristem size, cell division and stem elongation, floral induction, fruiting, and the flowering process, growth of the hypocotyl and stem, are all mediated by GA [121]. However, shoot elongation is by far the most significant physiological function of GA [122], which modifies the morphology of plants.
Cytokinins are a type of growth regulators that are responsible for seed germination, production of shoots, vascular cambium sensitivity, the proliferation of root hairs, improvement of cell division and root development, interactions of plants with pathogens, and nutrient mobilization and assimilation [123, 124], but suppress root elongation and lateral root formation [125, 126]. They are especially important for the cell cycle’s progression. Cytokinin, either alone or in combination with other phytohormones like abscisic acid and auxin, can help salt-stressed plants grow faster while also improving resistance by altering the expression of genes [127]. PGPRs, such as Bradyrhizobiumjaponicum, Azospirillumbrasilense, Pseudomonas fluorescens, Arthrobactergiacomelloi, Paenibacilluspolymyxa, and Bacillus licheniformis, have been demonstrated to produce cytokinin (particularly zeatin) [69]. Cytokinin-producing PGPRs act as biocontrol agents against a variety of pathogens [128].
PGPR has been proven in various investigations to be effective in both creating and regulating the amounts of ABA and gibberellic acid in plants. Gibberellins promote primary root elongation and lateral root development. Several PGPR, including Azotobacterspp, Azospirillumspp, Achromobacterxylosoxidans, Gluconobacterdiazotrophicus, Acinetobactercalcoaceticus, Bacillus spp., and Rhizobia spp., have been found to produce gibberellin [129].
The role of ABA under drought stress, for example, is well-known. Under conditions of water deficit, increased ABA levels cause stomata to shut, limiting water loss. This hormone, on the other hand, offers a variety of benefits during lateral root development [129]. Inoculation with Azospirillumbrasilense Sp245 increased ABA content in Arabidopsis, especially when grown under osmotic stress [130].
In addition to their roles in plant RSA, these two hormones are involved in plant defense mechanisms. As a result, PGPR, which produces these hormones, may affect the hormonal balance involved in plant defense, including the jasmonate and salicylic acid pathways [131].
As climate change conditions worsen, extreme environmental conditions that can cause significant annual losses in total crop output are now more prevalent worldwide [132, 133]. Many biotic and abiotic stresses are causing havoc on the sector, resulting in enormous plant productivity losses all around the world. Stress factors comprise nutrient shortages, heavy metal contamination, high wind, extreme temperatures, salinity, drought, illnesses, plant invasions, pests, salt, and soil erosion [69].
As a result of climate change, abiotic stresses, such as drought and high temperatures, have risen in frequency and intensity, resulting in 70% losses in major staple food crops, posing a danger to global food security [134]. Drought and high soil salinity, as well as their downstream impacts, such as osmotic, oxidative, and ionic stress, are regarded as important hindrances to long-term agriculture production [135]. Stressed plants suffer from internal metabolism disruption due to metabolic enzyme inhibition, substrate scarcity, excessive need for different chemicals, or a combo of the following. To endure unfavorable conditions, metabolic reconfiguration is required to comply with the demand for anti-stress compounds, such as suitable solutes, antioxidants, and proteins [136].
Agricultural breeding practices have tried to produce species that are more productive in unfavorable environments for ages. However, crop breeding for abiotic stress resistance has been impeded by a lack of reliable and consistent traits. Tolerance to stress is influenced by a number of genes working together. Furthermore, using agrochemicals to address biotic stresses and nutritional deficits contributes to environmental degradation, has a negative influence on the biogeochemical cycle system, and puts people at increased risk. The potential repercussions of the aforementioned stresses are significant, necessitating the development of robust, cost-effective, and environmentally acceptable methods to mitigate these stresses’ harmful effects on plants. As a result, there has been a spike in interest in environmentally friendly and organic agriculture techniques. Plant growth stimulants have been utilized in bio-fertilization, root revitalization, rhizoremediation, disease resistance, and other modes of microbial revival [137].
The efficient approach of PGPR can alleviate stresses that cause serious damage to crop yield, hence, the application of PGPR and/or their byproducts, which can help plants successfully resist extreme environmental circumstances, is one of the most eco-friendly ways [138]. Some PGPR genera, for instance, P. fluorescens, produce the enzymes 1-aminocyclopropane-1-carboxylate (ACC) deaminase and hydroxyacetophenone monooxygenase, which break down the ethylene precursor ACC to a-ketobutyrate and ammonia, thereby protecting plants from abiotic stressors [139]. The most destructive factors that reduce agricultural productivity are salinity and drought [140]. Furthermore, greater ethylene levels in the plant lead to premature fatuity symptoms, including leaf yellowing, abscission, and desiccation/necrosis [141]. PGPR is essential to minimize ethylene concentrations in plants, which in turn reduces stress.
During dry spells, turgor pressure and water potential have a significant impact on plant functionality. Drought stress results in substantial losses in agricultural output and the flow of nutrients, such as sulfates, nitrates, calcium, silica, and magnesium, as well as a reduction in photosynthesis activity [142]. To achieve sustainable agricultural productivity, bacterial colonies in the rhizosphere and endorhizosphere stimulate the plant to withstand drought [143]. PGPR releases osmolytes, which function in tandem with those obtained from plants to keep plants healthy and improve their growth and development, as well as withstand drought-related stress and excessive salt levels in the soil [144]. According to research findings, inoculating plants growing in dry and semi-arid areas with beneficial plant-growth-promoting rhizobacteria (PGPR), which enhances plant abiotic stress tolerance with an osmotic component, could improve drought tolerance and water utilization efficiency. PGPR-induced root development, nutrient uptake efficiency, and systemic tolerance have been proposed as biochemical changes in plants that result in increased abiotic stress tolerance (IST) [78].
Rise in global temperature and fluctuations in precipitation as a result of climate change have resulted in unprecedented crop pests and illnesses in various parts of the world [82]. Biotic agents, such as pathogenic bacteria, viruses, fungi, nematodes, protists, weeds, insects, and arachnids, are a prevalent concern in crop production and a long-term danger to sustainable agriculture and ecosystem stability around the world [145]. These species can induce biotic stress in their hosts by interfering with normal metabolism, injuring their plant hosts, reducing plant vigor, limiting plant development, and/or inducing plant mortality. Biotic stress has an impact on co-evolution, ecosystem nutrient cycling, population dynamics, horticulture plant health, and natural habitat ecology [146]. They also result in pre- and post-harvest damage to agricultural crops [147].
According to the FAO, pests are estimated to be responsible for up to 40% of global agricultural production losses each year. Plant diseases cost the world economy more than $220 billion per year while invading insects cost at least $70 billion [148].
Pesticides are chemical compounds that are used to prevent or control pests. However, these are poisonous compounds that pollute soil, watercourses, and plant life. The inappropriate application and overuse of such chemicals have triggered numerous problems (e.g., the emergence of resistance in target organisms, food contamination, and environmental pollution) [149]. Pesticide use causes morphological, physiological, biochemical, and molecular changes in plants that can have a detrimental effect on the plant’s development and growth, leaving chemical residues in numerous plant tissues, as well as insect resistance to pesticides [150, 151]. Besides, pesticides cause oxidative stress in plants, hinder physiological and biochemical pathways, cause toxicity, obstruct photosynthesis, and reduce crop yield. The overgeneration of reactive oxygen species has a negative effect on non-targeted plants. Reactive oxygen species are highly reactive in nature, causing oxidative damage to lipids, nucleic acids, proteins, carbohydrates, and DNA in plants, as well as disruptions in other biochemical and physiological cell processes [152].
The rising number and intensity of pesticide consumption have presented a significant obstacle to the pests being targeted, leading them to disseminate to dynamic habitats and/or adjust to the changing settings [153]. Resistance is currently the greatest serious impediment to the effective use of pesticides. Many pest species have developed resistance to pesticides as a result of their use around the World [154].
Pesticides’ impact on non-target species has been a source of debate and worry around the world for decades. Pesticides’ adverse impacts on non-target arthropods have been well documented [155]. Natural insect adversaries, such as parasitoids and predators, are tragically the most vulnerable to insecticides and suffer the most harm [156]. Natural enemies that ordinarily keep small pests in check are sometimes harmed, which can lead to subsequent pest outbreaks.
Not just that, pesticide use may have a negative impact on the earthworm population. Earthworms contribute to the improvement and maintenance of soil structure by producing channels in the soil that allow for aeration and drainage. In agricultural settings, they are regarded as a key indicator of soil quality [157]. Earthworms are harmed by a wide range of agricultural practices, with indiscriminate pesticide usage being one of the most serious [158]. Yasmin and D’Souza [159] found that pesticides have a dose-dependent effect on earthworm reproduction and proliferation.
Moreover, pesticide usage has the potential to destroy biodiversity. Degraded pesticides interface with the soil as well as its inhabitants, affecting microbial diversity, biochemical processes, and enzyme activity [160]. Any change in the activity of soil microorganisms as a result of pesticide application disrupts the ecological environment, resulting in a loss of soil quality. In crops cultivated on soils excessively exposed to chemical pesticides, nutrient loss and disease incidence are widespread [161], which is unfavorable from the perspective of agricultural soil management for food and nutritional security.
Exogenous pesticide residues may also alter the efficacy of beneficial root-colonizing microbes, such as fungi, bacteria, algae, and arbuscular mycorrhiza (AM), in soil by affecting their growth, and metabolic activity, among other things [162].
Furthermore, pesticides are widely distributed when they are transported across long distances by air or water [163]. Several pesticides have a prolonged half-life (up to years) in the environment; for example, the half-life of HCH in water is determined to be 191 days [164], hence posing a threat to aquatic creatures.
The mode of pesticides’ action is hazardous not just to the target organisms but also to non-target creatures, such as humans. The physicochemical parameters of the active ingredient are known to influence pesticide diffusion into plant tissue. As a result, pesticides with a systemic effect are absorbed by the roots or leaves and transported throughout the plant, as a result, they pose a major health risk to anyone who consumes them [165]. Pesticides’ negative impacts on human health have begun to emerge as a result of their toxicity, longevity in the environment, and tendency to penetrate the food chain. Based on the side effects, chemical pesticides employed in crop protection to limit the damage caused by pathogens and pests in agricultural areas pose significant long-term risks and challenges to life forms. Pesticides can penetrate the human body through immediate exposure to chemicals, contaminated water, or polluted air, as well as through food, particularly fruits and vegetables. Pesticide exposure can cause both acute and chronic disorders. Humans develop chronic sickness after being exposed to sub-lethal levels of pesticides for extended periods of time [166]. They are believed to stimulate cancer [167] and fetal malformations [168], and they are nonbiodegradable [169]. Encountering pesticides with genetic makeup, resulting in DNA damage and chromosomal abnormalities, is one of the primary pathways that lead to chronic disorders, such as cancer [170]. Pesticides can also cause oxidative stress by modifying the amounts of antioxidant enzymes, including glutathione reductase, superoxide dismutase, and catalase, which increase reactive oxygen species (ROS) [171]. Pesticide-induced oxidative stress has been linked to a number of health concerns, including Parkinson’s disease and glucose homeostasis disruption [170].
Given the pervasive harmful effects of pesticides on plants, soil, the environment, and human health, an environmentally friendly replacement is required, making PGPR a viable option.
Biocontrol agents are bacteria that suppress the occurrence or severity of plant diseases, whereas antagonists are bacteria that have antagonistic behavior toward a pathogen. PGPR can be used as a biocontrol agent (Figure 3) to protect plants from pathogens, such as viruses, bacteria, insects, and fungi [173].
PGPR as biocontrol agent [
When compared to chemical pesticides, PGPR has unique benefits, including being harmless to mankind and nature, dissolving more quickly in soil, and having a lesser possibility of pathogen resistance development [174]. Because plants, unlike animals, are unable to use avoidance and escape as stress-relieving strategies, their existence has been marked by the establishment of extraordinarily favorable partnerships with their more mobile partners, microbes. PGPR and its interactions with plants are economically harnessed [175], and they hold considerable promise for long-term agricultural sustainability. Plants that have been inoculated by immersing their roots or seeds in PGPR cultures overnight have been shown to be extremely resistant to many forms of biotic stress [176].
Antibiotic synthesis is one of the most robust and well-studied biocontrol mechanisms of PGPR against phytopathogens during the last two decades [177]. Antibiotics are low-molecular-weight toxins that have the ability to kill or inhibit the growth of other bacteria. The Bacillus genus and Rhizobacteria are the most significant for antibiotic synthesis [178]. Antibacterial and antifungal antibiotics are produced by Bacillus amyloliquefaciens and B. subtilis, including subtilin, bacilysin, and emicobacillin [179].
Induced systemic resistance (ISR) is a physiological condition of increased defensive capacity triggered by a specific environmental stimulation. Conrath et al. [180] define ISR as “an enhanced defensive ability of plants in response to specific pathogens stimulated by beneficial microorganisms present in the rhizosphere,” a scenario wherein the interaction of certain microorganisms with roots results in plant tolerance to pathogenic bacteria, fungi, and viruses. ISR can also be induced by certain environmental cues that cause upregulation of plants’ innate defenses in response to the biotic assault, allowing plants to respond faster and stronger to subsequent pathogen attacks [181]. Following the pathogenic invasion, signals are produced, and a defense mechanism is activated via the vascular system. Among the defense mechanisms produced by ISR in plants are cell wall reinforcement [182], production of secondary metabolites, and accumulation of defense-related enzymes, such as chitinases, glucanases, peroxidase, phenylalanine ammonia-lyase, and polyphenol oxidase, lipoxygenase, SOD, CAT, and APX along with some proteinase inhibitors [183].
ISR is not unique to a particular pathogen but can benefit a plant by evading a variety of diseases. Various plants develop systemic resistance to a wide range of plant diseases and a variety of environmental stresses when primed with PGPR [184]. ISR is among the pathways through which PGPR might minimize the onset of various plant diseases by modifying the physical and biochemical attributes of host plants and thereby boosting plant growth [185]. After applying plant-growth-promoting rhizobacteria, diseases of fungal, bacterial, and viral origin, as well as damage caused by insects and nematodes, can be decreased [186].
Non-pathogenic microorganisms promote ISR, which starts in the roots and extends to the shoots [187]. ISR stimulates plant defense mechanisms and shields unexposed regions of plants against future pathogenic attacks by microbes and insects. The signaling of ethylene and jasmonic acid in the plant is involved in induced systemic resistance, and these hormones increase the host plant’s defense responses against a range of plant diseases [188]. Lipopolysaccharides (LPS), siderophores, homoserine lactones, 2, 4-diacetylphloroglucinol, cyclic lipopeptides, and volatiles like acetoin and 2, 3-butanediol are only a few of the bacterial components that cause induced systemic resistance [189].
Plant-growth-promoting rhizobacteria use another mechanism to promote growth—enzymatic activity, producing compounds that inhibit phytopathogenic agents [190]. Rhizobacterial strains that promote plant growth can secrete enzymes, including ACC-deaminase, phosphatases, chitinases, 1,3-glucanase, proteases, dehydrogenases, and lipases, among others [94, 191]. They excrete cell wall hydrolases, which are used to break down cell walls, neutralize infections, assault pathogens, and cause hyperparasitic activity [192]. Plant-growth-promoting rhizobacteria suppress pathogenic fungi, such as
In recent years, microbial volatile organic compounds (mVOC) have been shown to play an important role in microorganism–plant interactions [196, 197, 198]. VOCs are produced by a wide range of soil microorganisms. Bacillus bacteria are the most common microbes that produce antimicrobial MVOCs. Bacterial volatiles have a key function in encouraging plant growth by regulating phytohormone synthesis and metabolism.
They can also promote plant health by acting as antibacterial, nematicidal, oomyceticidal, and antifungal agents, as well as eliciting plant immunity via the salicylic acid (SA) and jasmonic acid (JA) pathways [199]. These molecules have the potential to increase plant growth and development and induce systemic resistance (ISR) against pathogenic organisms, resulting in improved agricultural well-being [200]. Through the SA-signaling pathway, acetoin from the bacteria B. subtilis produces systemic resistance in
Depending on the species, the quantity and composition of VOCs varies [202]. 2, 3-Butanediol is a volatile organic compound (VOC) generated by a variety of microorganisms that, among other things, can activate plant resistance against pathogens. This mVOC generated by
The antagonistic activity of PGPR also results in the production of volatile compounds. HCN, a well-studied biocontrol agent, commonly known as prussic acid, is a broad-spectrum volatile secondary metabolite generated by numerous rhizobacteria and is crucial for the biological control of several infectious microorganisms in the soil. Most metalloenzymes are inhibited by their cyanide ion, particularly copper-containing cytochrome c oxidases [204]. HCN-producing Pseudomonas strains are employed in the biological control of tomato bacterial canker [205]. For instance, the inhibition of Macrophomina phaseolina and Meloidogyne javanica caused sunflower charcoal rot and tomato root-knot diseases and has been related to bacterial strains secreting HCN [206]. The inhibitory activity process starts in the mitochondria, where HCN inhibits electron transport, reducing energy supply to the cell and finally causing pathogenic organisms to die.
Plants generate a lot of “stress ethylene” (ET) after the onset of a disease or stress. Much of the growth inhibition that happens as a result of environmental stress is due to the plant’s response to elevated levels of stress ethylene, which aggravates the stressor’s response. Likewise, ethylene production inhibitors can considerably reduce the intensity of various environmental stressors. The production of defense enzymes, including 1-aminocyclopropane-1-carboxylate (ACC) deaminase, has also been linked to PGPM’s ability to protect against biotic stress [207]. Numerous results suggest that seed inoculation with bacterial endophytes increases plant defense. This is because bacteria produce the enzyme 1-aminocyclopropane-1-carboxylate (ACC), which can cleave ET into ketobutyrate and ammonia, lowering the presence of this enzyme linked to plant stress and physiological impairment [208]. As a result, if ACC deaminase-containing bacteria can reduce plant ethylene levels, treating plants with these organisms may give some defense against the stress inhibitory effects. The synthesis of ACC-deaminase by
To meet the ever-increasing nutritional demand of the rapidly increasing world population, chemical fertilizers must be employed. However, unintended and excessive use has a variety of negative repercussions on the natural environment resulting in soil degradation, global warming, and climate change, necessitating the search for environmentally sound alternatives. PGPR, in this regard, is a realistic choice for agricultural production that does not deplete natural resources. Plants and microbial communities in the soil have evolved a variety of biotic connections, ranging from commensalism to mutualism. Plant-PGPR collaboration is an important aspect of this web of interactions, promoting the growth and health of a variety of plants. PGPR has recently received a lot of attention for its potential to replace agrochemicals for plant growth and yield through a variety of processes, including decomposition of organic matter, recycling of essential elements, formation of soil structure, production of numerous plant growth regulators, fixation of atmospheric nitrogen, degradation of organic pollutants, stimulation of root growth, solubilization of phosphorus, production of siderophore, and solubilization of mineral nutrients, all of which are important for soil and plant health. Furthermore, they are cost-efficient and environmentally sustainable and assure that nutrients from natural sources are always accessible. Besides, bacterial colonies in the rhizosphere have a considerable impact on phytopathogenic microorganism reduction, in addition to boosting plant growth through active processes, hence the use of phytomicrobiome representatives in farming production as long-term disease prevention and nutrient supplement strategy could also help to mitigate the detrimental effects of pesticide use.
As a nutshell, in the face of global climate change, PGPR could be a more environmentally friendly option than chemical fertilizers.
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",metaTitle:"IntechOpen events",metaDescription:"In our mission to support the dissemination of knowledge, we travel worldwide to present our publications, authors and editors at international symposia, conferences, and workshops, as well as attend business meetings with science, academia and publishing professionals. We are always happy to host our scientists in our office to discuss further collaborations. Take a look at where we’ve been, who we’ve met and where we’re going.",metaKeywords:null,canonicalURL:"/page/events",contentRaw:'[{"type":"htmlEditorComponent","content":"May 18, 2022 | 1:00 PM - 2:00 PM CEST
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May 18, 2022 | 1:00 PM - 2:00 PM CEST
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19 - 23 October 2022, Frankfurt, Germany
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