Feasible sources and characterization of adult stem cells
\\n\\n
IntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\\n\\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\\n\\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\\n\\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\\n\\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\\n\\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\\n\\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\\n\\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\\n\\nFeel free to share this news on social media and help us mark this memorable moment!
\\n\\n\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/237"}},components:[{type:"htmlEditorComponent",content:'
After years of being acknowledged as the world's leading publisher of Open Access books, today, we are proud to announce we’ve successfully launched a portfolio of Open Science journals covering rapidly expanding areas of interdisciplinary research.
\n\n\n\nIntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\n\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\n\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\n\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\n\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\n\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\n\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\n\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\n\nFeel free to share this news on social media and help us mark this memorable moment!
\n\n\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{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"}]},book:{item:{type:"book",id:"1977",leadTitle:null,fullTitle:"Emerging Informatics - Innovative Concepts and Applications",title:"Emerging Informatics",subtitle:"Innovative Concepts and Applications",reviewType:"peer-reviewed",abstract:"The book on emerging informatics brings together the new concepts and applications that will help define and outline problem solving methods and features in designing business and human systems. 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Nascimento",coverURL:"https://cdn.intechopen.com/books/images_new/8137.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"64160",title:"Prof.",name:"Simona",middleName:null,surname:"Clichici",slug:"simona-clichici",fullName:"Simona Clichici"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},ofsBook:{item:{type:"book",id:"11919",leadTitle:null,title:"SQL Programming in Practice",subtitle:null,reviewType:"peer-reviewed",abstract:"
\r\n\tNowadays, all types of businesses ranging from the smallest e-com stores to the biggest corporations, use data to run operations. There are billions of bytes of data getting generated every minute. However, raw data doesn’t come in that handy on its own. There are many data management tools and applications. SQL or Structured Query Language is one of the programming languages which is used to communicate with the databases for the creation, deletion, and retrieval of data from it. The ability to use SQL will help you get more out of your data than just reading it. It can be used for ad-hoc data analysis and reporting and more extensive projects involving multiple tables and complex applications.
\r\n\r\n\t
\r\n\tSQL is worth learning because it’s a programming language that’s in demand in the tech industry and in other sectors that need technology. Most software developers who know SQL earn respectable salaries. Learning SQL can not only enhance your skills, but it can also give you a better understanding of the applications you work with daily. In this book, we will go through the details of SQL and how to use it effectively. The goal of this book is to have many practical application examples that will help learners easily acquire and self-study SQL.
Stem cells are undifferentiated cells defined by their abilities to self-renew and differentiate into mature cells. Stem cells found in fully developed tissues are defined as adult stem cells. The function of adult stem cells is the maintenance of adult tissue specificity by homeostatic cell replacement and tissue regeneration (Wagers and Weissman, 2004). Adult stem cells are presumed quiescent within adult tissues, but divide infrequently to generate a stem cell clone and a transiently-amplifying cell. The transiently-amplifying cells will undergo a limited number of cell divisions before terminal differentiation into mature functional tissue cells. The existence of adult stem cells has been reported in multiple organs; these include: brain, heart, skin, intestine, testis, muscle and blood, among others. This chapter focuses on four adult stem cell populations: hematopoietic, mesenchymal, periodontal ligament-derived, and spermatogonial (Table 1).
Hematopoietic stem cells are the most characterized adult stem cell population. They function to generate all cell lineages found in mature blood (erythroid, myeloid and lymphoid) and to sustain blood production during the entire life of an animal (Kondo et al., 2003). Adult bone marrow, umbilical cord blood and mobilized peripheral blood are sources of hematopoietic stem cells for transplantation in many blood-related diseases. Hematopoietic stem cells can be characterized by positive selection of CD34, CD45, and CD133 markers and negative selection of CD31, CD105 and CD146 markers (Tárnok et al., 2010).
Mesenchymal stem cells, also called marrow stromal cells, are another well-studied adult stem cell population. Mesenchymal stem cells were originally identified in the bone marrow, but have since been found in other systems such as adipose tissue, umbilical cord and menstrual blood (Ding et al., 2011). Mesenchymal stem cells differentiate into osteocytes, chondrocytes and adipocytes (Arita et al., 2011; Pittenger et al., 1999). Human mesenchymal stem cells can be characterized by the positive expression of CD29, CD44, CD73, CD90, CD105, CD146 and STRO-1, and the negative expression of CD31, CD34, CD45, CD49f and CD133 (Mödder et al., 2012; Tárnok et al., 2010).
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
Hematopoietic stem cells | \n\t\t\tBone marrow, umbilical cord blood, mobilized peripheral blood | \n\t\t\t(+): CD34, CD45, CD133 | \n\t\t
(-): CD31, CD105, CD146 | \n\t\t||
Mesenchymal stem cells | \n\t\t\tBone marrow, adipose tissue, umbilical cord, menstrual blood | \n\t\t\t(+): CD29, CD44, CD73, CD90, CD105, CD146, STRO-1 | \n\t\t
(-): CD31, CD34, CD45, CD49f, CD133 | \n\t\t||
Periodontal ligament-derived stem cells | \n\t\t\tPeriodontal ligament | \n\t\t\tMesenchymal stem cell markers: CD29, CD44, CD73, CD90, CD105, CD146, STRO-1 | \n\t\t
Neural crest cell markers: p75, nestin, Slug, SOX10 | \n\t\t||
Spermatogonial stem cells | \n\t\t\tTestis | \n\t\t\t(+): CD9, CD49f and GPR125 | \n\t\t
Feasible sources and characterization of adult stem cells
Periodontal ligament, derived from the cranial neural crest, is a soft connective tissue embedded between the tooth root and the alveolar bone socket, supporting the teeth
Testicular spermatogonial stem cells are the germ-line cells for spermatogenesis, an ongoing process throughout the lifespan of the male animals. They are unipotent in nature and continuously generate differentiating daughter cells for subsequent production of spermatozoa (Fagoonee et al., 2011). Human spermatogonial stem cells can be purified by antibodies against cell surface markers CD9, CD49f and GPR125 (Conrad et al., 2008).
Pluripotency refers to the ability of cells to self-renew and differentiate into all 3 germ layers (ectoderm, endoderm and mesoderm). Pluripotent stem cells are the origin of all somatic and germ-line cells in the developing embryo. The first pluripotent cells were derived in 1976 from a type of germ-line tumor known as a teratocarcinoma (Hogan, 1976). Embryonic stem cells, derived from the inner cell mass of a blastocyst prior to gastrulation, are still considered the gold standard for pluripotent stem cells. Even though adult cells are terminally differentiated, pluripotency has also been conferred to these cells in past studies, by the technique of somatic cell nuclear transfer (Perry, 2005), parthenogenesis of unfertilized eggs (Brevini et al., 2008), and reprogramming by cell fusion (Pralong et al., 2006). Research into adult cell pluripotency was slow to progress until a major breakthrough in 2006 brought with it the technique of “induced pluripotent stem cells”. In this process adult skin fibroblasts were induced into a pluripotent state by the forced expression of key transcription factors (OCT4, SOX2, KLF4 and c-MYC; Takahashi et al., 2007) or (OCT4, SOX2, NANOG and LIN28; Yu et al., 2007). Despite the low reprogramming efficiency, this has become a convenient method for generating new pluripotent stem cell lines for research from differentiated adult cells.
Adult stem cells are thought to be tissue-specific and only able to differentiate into progeny cells of their tissues of origin. An increasing number of studies, however, report that adult stem cells are capable of giving rise to cells of an entirely distinct lineage. The concept of adult stem cell plasticity might be explained by 5 potential mechanisms: cell fusion, trans-differentiation, de-differentiation, heterogeneous stem cell populations, or pluripotency (Wagers and Weissman, 2004). Cell-cell fusion occurs at a low frequency, but is implicated in the transplantation of bone marrow cells to liver hepatocytes, cardiomyocytes and Purkinje neurons (Alvarez-Dolado et al., 2003). In cell fusion events, the stem cells acquire the mature phenotype of the tissue they are embedded within and can be easily mistaken for correct differentiation of the transplanted cells. Trans-differentiation is a direct lineage conversion by the activation of a dormant differentiation program to alter the lineage specificity of the cell. De-differentiation is another lineage conversion phenomenon in which a tissue-specific cell spontaneously de-differentiates into a more basal multipotent cell and re-differentiates to a new lineage. While the heterogeneity of the stem cell population employed can account for some of the apparent trans-differentiation and de-differentiation events observed
The expression of embryonic stem cell markers in some adult stem cells suggest a sub-population of pluripotent cells in these niches (Table 2). The common embryonic stem cell makers, such as OCT4, SOX2, NANOG, KLF4, LIN28, SSEA-1, SSEA-3, SSEA-4, TRA-1-60 and TRA-1-81, are all expressed in hematopoietic stem cells (Wang et al., 2010; Zhao et al., 2006; Zulli et al., 2008) and mesenchymal stem cells (Anjos-Afonso and Bonnet, 2007; Jaramillo-Ferrada et al., 2012; Riekstina et al., 2009; Sung et al., 2010). Similarly, expressions of most of these markers, except for LIN28, have been reported in periodontal ligament-derived stem cells, a tissue arising from the migrating cranial neural crest (Huang et al., 2009; Kawanabe et al., 2010). Previous studies show that spermatogonial stem cells also express most of the embryonic stem cell markers, except SSEA-3 and TRA-1-60 (Izadyar et al., 2008; Izadyar et al., 2011; Kanatsu-Shinohara et al., 2008; Panda et al., 2011; Zheng et al., 2009). These findings suggest that pluripotent stem cells exist as sub-populations in adult stem cell reservoirs.
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
SOX2 | \n\t\t\t+ | \n\t\t\t+ | \n\t\t\t+ | \n\t\t\t+ | \n\t\t
OCT4 | \n\t\t\t+ | \n\t\t\t+ | \n\t\t\t+ | \n\t\t\t+ | \n\t\t
NANOG | \n\t\t\t+ | \n\t\t\t+ | \n\t\t\t+ | \n\t\t\t+ | \n\t\t
KLF4 | \n\t\t\t+ | \n\t\t\t+ | \n\t\t\t+ | \n\t\t\t+ | \n\t\t
LIN28 | \n\t\t\t+ | \n\t\t\t+ | \n\t\t\t\n\t\t\t | + | \n\t\t
SSEA-1 | \n\t\t\t+ | \n\t\t\t+ | \n\t\t\t+ | \n\t\t\t+ | \n\t\t
SSEA-3 | \n\t\t\t+ | \n\t\t\t+ | \n\t\t\t+ | \n\t\t\t\n\t\t |
SSEA-4 | \n\t\t\t+ | \n\t\t\t+ | \n\t\t\t+ | \n\t\t\t+ | \n\t\t
TRA-1-60 | \n\t\t\t+ | \n\t\t\t+ | \n\t\t\t+ | \n\t\t\t\n\t\t |
TRA-1-81 | \n\t\t\t+ | \n\t\t\t+ | \n\t\t\t+ | \n\t\t\t+ | \n\t\t
Embryonic stem cell marker expression in different adult stem cell populations
HSC: hematopoietic stem cells; MSC: mesenchymal stem cells; PDLSC; periodontal ligament-derived stem cells; SSC: spermatogonial stem cells;
The existence of cells with a defined pluripotency-associated phenotypic expression within adult tissues enables researchers to isolate and purify a homogeneous subpopulation of adult pluripotent stem cells. In fact, with the use of magnetic affinity cell sorting, adult human mesenchymal stem cells, shown to differentiate into endodermal, ectodermal and mesodermal cells, were isolated by antibody against SSEA-3 (Kuroda et al., 2010). Similarly, stem cells exhibiting the potential to generate specialized cells of the three embryonic germ layers can be isolated by positive SSEA-4 expression from human periodontal ligament (Kawanabe et al., 2010). Furthermore, human spermatogonial stem cells, sharing cellular and molecular similarities with human embryonic stem cells, can be purified by α6 integrin (CD49f) antibody (Conrad et al., 2008). Moreover, a human hematopoietic stem cell subpopulation, highly efficient in generating long-term multi-lineage grafts, can also be isolated by the same α6 integrin expression (Notta et al., 2011). In addition, stem cells from granulocyte colony-stimulating factor-mobilized human peripheral blood can divide indefinitely without reaching replicative senescence and differentiate into multiple lineages (Cesselli et al., 2009).
Recently, a cell surfaceome map of mouse embryonic stem cells and induced pluripotent stem cells was reported (Gundry et al., 2012). Previously unidentified cellular surface markers, such as CD31, CD49f, CD123 and CD326, indicated a purified population of pluripotent stem cells. Further analyses should be performed to determine the expression of these markers in different adult stem cell populations. Their presence in adult stem cell populations could facilitate the purification of homogeneous pluripotent stem cells within an otherwise heterogeneous pool of regenerative adult cells.
The standard tests for pluripotency are teratoma and chimera formation assays. Teratomas can be formed when pluripotent stem cells are injected into immunodeficient animals; they consist of foci with derivatives of ectodermal, mesodermal and endodermal embryonic germs layers (Wobus et al., 1984). Chimeras can be generated when pluripotent stem cells are microinjected into mouse blastocysts and are induced to differentiate into multiple cell types during normal developmental processes (Becker et al., 1984). Teratoma formation assays can be used to test for the pluripotency of human stem cells, whereas both teratoma and chimera formation can test for the pluripotency of mouse stem cells. Spermatogonial stem cells isolated from human testis by positive expression of CD49f are able to form teratomas when injected into immunodeficient mice (Conrad et al., 2008). Mesenchymal stem cells isolated from murine bone marrow contribute to most of the somatic cell types (chimerism ranged between 0.1% and 45%) when they are singly injected into an early mouse blastocyst (Jiang et al., 2002). Moreover, human hematopoietic stem cells isolated by CD49f cell surface marker display multi-lineage chimerism when transplanted into the NOD-
Although most of the adult stem cells are unable to form teratomas in immunodeficient mice, can they still be defined as pluripotent stem cells? Considering this apparent inability as well as the variability in teratoma formation efficiency even when using a known pluripotent stem cell line, a teratoma assay might not be a suitable assay for pluripotency of adult stem cells. Instead,
Human embryonic stem cells come from the inner cell mass of human blastocysts. Therefore, embryonic stem cells used for cell therapy are allogenic; the transplanted donor cells do not originate from the recipient. This raises a concern about the immunogenic response of the host, and the need for immune-suppressive therapy concurrent with embryonic stem cell transplantation (Charron et al., 2009). Moreover, embryonic stem cell-based therapy has been hampered by the moral, legal and ethical dilemma surrounding the use of human embryos for derivation of the stem cell lines (Zarzeczny and Caulfield, 2009). Furthermore, as the gold standard of pluripotent stem cells, embryonic stem cells have the potential to form teratomas in the host. Tumorigenic potential can be reduced by differentiating the embryonic stem cells into lineage-specific progenitor cells or mature tissue cells prior to transplantation (Schwartz et al., 2012). In order to better control standards of good manufacturing practices and reduce variability as much as possible, the
Differentiated adult cells used for the generation of the induced pluripotent stem cells can be collected from the recipient body, avoiding the contentious need for a human embryo. This also circumvents the problem of immune rejection. There are technical hurdles, however, concerning generation of induced pluripotent stem cells (Hayden, 2011). Firstly, the delivery of reprogramming factors (OCT4, SOX2, NANOG, LIN28, KLF4 and c-MYC) relies on the use of viral vectors for delivery (Takahashi et al., 2007). Retroviral sequences could integrate into the DNA of the host cells, potentially disrupting the gene structure as well as resulting in an aberrant phenotypic expression. Ultimately this could result in pathological mutations and cancer formation. Alternative methods such as direct protein or small molecule delivery have been adopted, although the reprogramming efficiency of these techniques is lower than with viral vectors (Kim et al., 2009; Shi et al., 2008). Secondly, two of the reprogramming factors,
The sources of adult stem cells are multiple and feasibly obtained from various adult tissues, such as bone marrow, blood, adipose tissue, teeth and testes (Table 1). These adult stem cells can be collected from the human body at anytime throughout life. This makes them readily available and does not raise the moral and ethical issues involved with the attainment of embryonic stem cells. Moreover, pluripotent adult stem cells can easily be isolated and purified by cell surface markers, such as CD49f, SSEA-3 and SSEA4 (Conrad et al., 2008; Kuroda et al., 2010; Kawanabe et al., 2010; Notta et al., 2011). The pluripotent status of these adult stem cells is naturally acquired and does not require reprogramming by the introduction of pluripotent transcriptional factors, thus eliminating the use of viral vectors and the chance of aberrant chromosomal changes. Furthermore, transplantation of mesenchymal stem cells and periodontal ligament-derived stem cells can be autogenic or allogeneic. Immuno-suppression is not necessary since mesenchymal stem cells have strong immunomodulatory properties against alloreactivity of T lymphocytes and dendritic cells (Chen et al., 2011). Similarly, mesenchymal stem cells and periodontal ligament-derived stem cells inhibit the proliferation of peripheral blood mononuclear cells (Wada et al., 2009). Spermatogonial stem cells, however, are killed by cytotoxic T lymphocytes after transplantation (Dressel et al., 2009), whereas allogeneic hematopoietic stem cell transplantation induces graft-vs-host disease (Strober et al., 2011). Therefore, transplantation of spermatogonial stem cells and hematopoietic stem cells should only be autogenic, without the application of immunosuppressive drugs. Similar to embryonic stem cells and induced pluripotent stem cells, pluripotent adult stem cells can differentiate into specialized cells of the three germ layers. Except for spermatogonial stem cells (Conrad et al., 2008), teratoma formation was not found in pluripotent hematopoietic stem cells, mesenchymal stem cells and periodontal ligament-derived stem cells (Kuroda et al., 2010; Kawanabe et al., 2010; Notta et al., 2011). This suggests a reduction in the probabilities of tumor formation post-transplantation, and the elimination of the need to manipulate the cells into mature tissue prior to transplantation. In addition, transplanted stem cell-induced regeneration may not be due to stem cell differentiation per se (Johnson et al., 2010; Williams and Hare, 2011). Instead, a paracrine effect has been hypothesized in which the adult stem cells secrete cytokines, chemokines, or protective proteins (Bai et al., 2012; Bráz et al., 2012) that nourish the host tissue cells and facilitate the healing process. This special feature has not yet been reported with the use of embryonic stem cells or induced pluripotent stem cells in a clinical setting.
Stem cell clinical trials have advanced rapidly for a broad spectrum of diseases, such as diabetes, neurodegeneration, immune diseases, heart disease, and bone disease. In 2011, there were 123 clinical trials using mesenchymal stem cells (Trounson et al., 2011). It is predicted that stem cell therapy will eventually become the treatment of choice in regenerative medicine, especially the use of adult stem cells. As stem cell products become more wide-spread and maintained under various conditions, the need for global standardization and regulation of processes will become necessary for the viable application of these products in a clinical setting. The Food and Drug Administration regulates interstate commerce in human cells and tissue-based products under the Public Health Service Act and the Code of Federal Regulations for Food and Drugs (Lysaght and Campbell, 2011). Human cells and tissue-based products are defined as “articles containing or consisting of human cells or tissues that are intended for implantation, transplantation, infusion, or transfer into a human recipient” (Lysaght and Campbell, 2011). Human cells and tissue-based products must be: (1) minimally manipulated, (2) intended only for homologous use, (3) not combined with another article (except for water, or sterilization, preservation, or storage agents), and (4) either: (a) have no systemic or metabolic effect, or (b) be for autologous use, allogeneic use in first- or second-degree blood relative, or reproductive use.
Pluripotent adult stem cells fall under the criteria for human cells and tissue-based products as stated by the Food and Drug Administration. Unlike induced pluripotent stem cells, pluripotent adult stem cells can be minimally manipulated as their pluripotent state occurs naturally. Unlike embryonic stem cells, pluripotent adult stem cells are suited for autologous use. Similar to embryonic stem cells and induced pluripotent stem cells, pluripotent adult stem cells are able to differentiate into specialized cells of the three germ layers. In addition, embryonic stem cells and induced pluripotent stem cells have the potential to form teratomas (an unfavorable side-effect in clinical applications) although a recent study suggests that the teratoma-forming cells could be removed by the antibody against SSEA-5 (Tang et al., 2011). In contrast, most pluripotent adult stem cells do not form teratomas
If stem cell-aided regeneration is not due to stem cell differentiation to replace damaged cells (Johnson et al., 2010; Williams and Hare, 2011), pluripotent adult stem cells are favorable over embryonic stem cells and induced pluripotent stem cells. The secretion of cytokines, chemokines, and/or protective proteins from the adult stem cells could nourish the host tissue and facilitate the healing process (Bai et al., 2012; Bráz et al., 2012).
Adult stem cells are found all over the body. They can be conveniently obtained from different accessible tissues: bone marrow, blood, adipose tissue, teeth and testes. Pluripotent adult stem cells, which reside as a subpopulation within adult stem cells, can be easily isolated by pluripotent cell surface markers, such as SSEA-3, SSEA-4 and CD49f. Moreover, pluripotent adult stem cells can be characterized by their ability to differentiate into cells of 3 germ layers (ectoderm, mesoderm and endoderm) as well as by the chimera formation in xeno-transplanted mice. Pluripotent adult stem cells are better than embryonic stem cells and induced pluripotent stem cells as they are an autologous source, require minimal manipulation and do not have the ability to form teratomas. In addition, they are more appropriate to be used as a clinical product for therapeutic treatments, as a cellular replacement or secretory protein reservoir. However, there are uncertainties that still remain unanswered. Which stem cell types are optimal for regenerative medicine? What is the optimal cell number for transplantation? Should the cells be preemptively differentiated or used as is? Further research is needed to understand the mechanisms of stem cells in regenerating damaged tissues after transplantation.
The first isolation of
Compared to other gastrointestinal (GI) segments, the stomach has a physiological environment that is significantly more hostile to bacterial colonization and is a crucial part of the dynamics of the gastric microbiota. Primary reason for this is the gastric juice, which is composed of two main components—proteolytic enzymes and hydrochloric acid (HCl). The hydrochloric acid creates a strong acidic environment by maintaining a pH of 1–2 in the gastric lumen, which together with the proteolytic features of the gastric enzymes creates an intragastric environment that serves both digestive and protective roles. This environment facilitates the denaturation of proteins and nutrient absorption but also severely limits bacterial colonization and survival, preventing infection by pathogens [4]. The low pH value is the main restrictive component of the gastric juice [5]. To prevent damage to the mucosa from the acid and enzymes, neck cells of the gastric glands secrete mucus on the surface of the gastric epithelium. This mucus layer establishes a pH gradient that increases the pH up to 6–7 at the surface of the mucosa [6]. This is due to the unique properties of the mucus which permit acid to flow from parietal cells into crypts which communicate with the lumen, but do not allow acid at pH <4 from penetrating the mucus layer [6]. The mucus layer consists of several different mucin molecules, including MUC1, MUC5AC, MUC5AB, and MUC6, and forms two sublayers, an inner mucus layer that is firmly attached to the epithelia and a loose mucus layer, which is in direct contact with the lumen [7, 8]. Additional factors that contribute to the strong antimicrobial environment of the stomach are the accidental bile reflux and the gastric peristalsis.
In 1982
Initial studies on the bacteria present in the stomach, using culture-based techniques, such as gastric juice cultures and mucosal biopsies were reported even before the isolation of
Culture-independent studies use a variety of molecular methods based on 16S rRNA gene sequencing. A multitude of reasons define these methods as far superior to those which are culture-dependent. These include:
16S rRNA is present in almost all bacteria.
The function of the 16S rRNA gene has remained unchanged over time, suggesting that random sequence changes are a more accurate measure of time (evolution).
The 16S rRNA gene is large enough for computational purposes [24].
A variety of 16S rRNA based methods exist, including:
Fluorescent in situ hybridization (FISH) [25]
Dot-blot hybridization with rRNA-targeted probes [26]
Targeted qPCR [27]
Traditional or sequence-aided community fingerprinting [28]
Temperature gradient gel electrophoresis (TGGE) [29]
Terminal restriction fragment length polymorphism (T-RFLP) [30]
Sequencing of cloned 16S rDNA [29]
Microarrays (PhyloChip) [31]
Next-generation sequencing (NGS) [32]
In an extensive review of eight culture-independent studies, Sheh A. and Fox J. concluded that the most prominent phyla in the stomach are
Numerous studies have shown significant variability of the gastric microbial communities with respect to
Several mouse model studies have also shown clear differences in the composition of the gastric microbiota with respect to
A few studies have also examined
A few studies have given insight on how other microbial species can affect
As previously described
As described,
The human gastric juice has an interprandial pH of between 1 and 2 in the gastric lumen, whereas with food ingestion it can reach up to pH 5. pH also varies in the different anatomical regions of the stomach, with most acidic being the fundus and the least being the antrum. The mucus lining the gastric mucosa establishes also a pH gradient from the lumen to the surface of the epithelium. This mucus consists of two sublayers—an inner mucus layer that is firmly attached to the epithelium and a variable mucus layer directly interacting with the lumen [7, 8]. Thus, across the mucus layer, the pH ranges from about 5.5 to 6.8 or even 7 at the surface of the gastric epithelial cells [5, 6]. It was already discussed that the low pH, caused by the hydrochloric acid, restricts the quantity of microorganisms and reduces the risk of infection by pathogens. Hence, sites with higher pH are significantly more hospitable to colonization and have a higher microbial density. Considerable fluctuations in the microbial density have been described with respect to the pH in the stomach, whereby both the quantity and the proportion of genera also fluctuate [43, 44]. Bacteria and bacterial DNA, which are isolated from gastric juice, differ from bacterial isolates adhering to the mucosa. During abnormal conditions, this balance may be different.
While many studies document the effects of diet on the gut microbiota composition in humans, [45, 46, 47, 48, 49] there are only a few, mainly animal model studies, addressing the influence of diet on the gastric microbiota. An example is an in vivo study that compared the gastric microbiota of mice fed a non-purified diet (natural source-derived food) to mice fed a purified diet (refined food) and found higher levels of total aerobes, total anaerobes, and
The long-term use of proton pump inhibitors (PPIs) and H2 antagonists affects the composition of the gastric microbiota by inducing a non-
Antibiotics are well known to have suppressive effects on the gastrointestinal microflora.
The isolation of
Nevertheless, there is arising evidence that non-
Each year approximately 990,000 people are diagnosed with gastric cancer (GC) worldwide, of whom about 738,000 die from this disease, making GC the fourth most common incident cancer and the second most common cause of cancer death. Both incidence and mortality rates are about twice as high in males as in females. Over 70% of cases occur in developing nations, concentrated in Eastern Asia, Eastern Europe, and Central and South America. Approximately 90% of gastric cancers are adenocarcinomas, with the other 10% shared between mucosa-associated lymphoid tissue (MALT) lymphomas, gastrointestinal stromal tumors (GIST), leiomyosarcomas, and other more rare types of cancer. Adenocarcinomas are histologically classified into two major types: diffuse and intestinal. These two types not only look different under the microscope but also differ in gender ratio, age at diagnosis, and other epidemiologic features. Anatomically, gastric cancers are categorized as proximal and distal. Proximal adenocarcinomas are more similar to esophageal adenocarcinomas and may be associated with the absence of
However,
Studies with INS-GAS mice have revealed that male mice with intestinal microbiota developed gastric pathology from chronic gastritis to atrophy and dysplasia independent of
A study by Wang et al. found a similar number of bacterial species in the microbiota between gastric cancer and chronic gastritis, but by using a method to explore and visualize similarities or dissimilarities of the data, a pattern suggesting the presence of a diversified microbiota in gastric cancer was found [68]. Moreover, a 16S rRNA gene sequencing analysis of gastric mucosa of patients with gastric cancer showed a prevalence of the genera
It is possible that non-
The stomach is part of the GI tract, and as such, possible relations between the gastric microbiota’s composition and diseases of other parts of the GI tract, such as the esophagus (esophagitis and esophageal cancer), small intestines, and colon cannot be overlooked [72]. One study, using 16S rDNA analyses of duodenal aspirates, demonstrated lower diversity in irritable bowel syndrome patients compared to controls with significant alterations in 12 genera [73]. An increased risk for colorectal neoplasia in
Other studies have addressed the association between autoimmune hepatitis and altered microbiome of the upper GI tract and found this to be linked to increased intestinal permeability [76].
Regarding the extra-gastrointestinal involvement of gastric microbiota (especially
Nevertheless, research in this field is far from sufficient to be conclusive.
It is undeniable that
The publication of this work was supported by KRKA.
There are no conflicts of interest.
Intro
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When either or both of them are at a weak level, economic development is much lower.",book:{id:"9030",slug:"perspectives-on-economic-development-public-policy-culture-and-economic-development",title:"Perspectives on Economic Development",fullTitle:"Perspectives on Economic Development - Public Policy, Culture, and Economic Development"},signatures:"Kyriaki I. Kafka, Pantelis C. Kostis and Panagiotis E. Petrakis",authors:null},{id:"68007",doi:"10.5772/intechopen.85036",title:"Overview of the Process of Enzymatic Transformation of Biomass",slug:"overview-of-the-process-of-enzymatic-transformation-of-biomass",totalDownloads:1413,totalCrossrefCites:4,totalDimensionsCites:5,abstract:"Cellulase is an enzyme which depolymerizes the cellulose into glucose. Cellulases are produced by a diverse array of microbes including fungi, bacteria, yeast and actinomycetes. Considerable research for understanding the mechanism of cellulases began in early 1950s because of the significant use of these enzymes in various industries. This review provides a general account structure and availability of lignocellulosic biomass, pretreatment strategies for effective digestion, cellulase producing organisms, cellulase activity assay, and enzymology of cellulose degradation. Cellulase production, optimization, purification and characterization studies in addition to the industrial application of cellulase have also been discussed. At last a brief account of present market scenario of cellulases and future prospects of the study are also taken into account.",book:{id:"8150",slug:"elements-of-bioeconomy",title:"Elements of Bioeconomy",fullTitle:"Elements of Bioeconomy"},signatures:"Namita Singh, Anita Devi, Manju Bala Bishnoi, Rajneesh Jaryal, Avni Dahiya, Oleksandr Tashyrev and Vira Hovorukha",authors:[{id:"278205",title:"Prof.",name:"Namita",middleName:null,surname:"Singh",slug:"namita-singh",fullName:"Namita Singh"},{id:"282352",title:"Dr.",name:"Anita",middleName:null,surname:"Devi",slug:"anita-devi",fullName:"Anita Devi"},{id:"282353",title:"MSc.",name:"Avni",middleName:null,surname:"Dahiya",slug:"avni-dahiya",fullName:"Avni Dahiya"},{id:"282354",title:"MSc.",name:"Manju Bala",middleName:null,surname:"Bishnoi",slug:"manju-bala-bishnoi",fullName:"Manju Bala Bishnoi"},{id:"282355",title:"Dr.",name:"Oleksandr",middleName:null,surname:"Tashyrev",slug:"oleksandr-tashyrev",fullName:"Oleksandr Tashyrev"},{id:"282356",title:"Dr.",name:"Rajneesh",middleName:null,surname:"Jaryal",slug:"rajneesh-jaryal",fullName:"Rajneesh Jaryal"},{id:"282939",title:"Dr.",name:"Vira",middleName:null,surname:"Hovorukha",slug:"vira-hovorukha",fullName:"Vira Hovorukha"}]},{id:"56708",doi:"10.5772/intechopen.69096",title:"Human Development and Research-Development-Extension Relationships",slug:"human-development-and-research-development-extension-relationships",totalDownloads:1775,totalCrossrefCites:1,totalDimensionsCites:5,abstract:"Human capital is the most important strategic factor for development; as new technologies emerge, the market demand for better and healthier products and consumer demand in terms of quality and delivery time are changing. In today’s world, it becomes increasingly important to know how information can be accessed, how it is adopted, and how it can be assimilated. In this respect, each country allocates budget for training, education, and extension according to its own conditions. This budget may be intended for rural community-based social assistance, but the economic and welfare effect is essential. In this way, it is aimed to increase the living standards of the families living in the rural areas. This will naturally contribute to national income and to the prosperity of society. The subject has been discussed generally in the world, especially in the case of Turkey. According to this, all over the world, particularly in developing countries, research and extension (R&E) is very important and should be considered at least as much as research and development (R&D). However, it will be ensured that societies meet with the technology produced. For this, the development of human resources should be emphasized and a suitable atmosphere should be prepared for this widespread prosperity.",book:{id:"5819",slug:"research-and-development-evolving-trends-and-practices-towards-human-institutional-and-economic-sectors-growth",title:"Research and Development Evolving Trends and Practices",fullTitle:"Research and Development Evolving Trends and Practices - Towards Human, Institutional and Economic Sectors Growth"},signatures:"Orhan Özçatalbaş",authors:[{id:"170206",title:"Prof.",name:"Dr. Orhan",middleName:null,surname:"Özçatalbaş",slug:"dr.-orhan-ozcatalbas",fullName:"Dr. Orhan Özçatalbaş"}]},{id:"59430",doi:"10.5772/intechopen.74381",title:"Taxation and Economic Growth in a Resource-Rich Country: The Case of Nigeria",slug:"taxation-and-economic-growth-in-a-resource-rich-country-the-case-of-nigeria",totalDownloads:3916,totalCrossrefCites:3,totalDimensionsCites:4,abstract:"In this chapter, we examine the relationship between taxation and economic growth in a resource rich country, using Nigeria as a case study. We explore the linkages between availability of higher resource revenue and lower taxation effort of other revenue categories and the effects of these on growth. Ordinary least square (OLS) estimation technique is employed in estimating the specified model. Also, descriptive analysis is carried out regarding tax trends and tax efforts in Nigeria to determine the effectiveness of existing tax structures, as well to as examine relevant national and cross-country data. Empirical results reveal that taxation has a significant impact on Real GDP growth rates. However, the proportion of tax contribution to the growth rate falls short of the optimal level in terms of the volume of economic activities and value of total output. Nigeria also lags other African countries with respect to tax effort and as such has a huge untapped potential for enhanced revenue mobilisation. We recommend therefore, that the Government should institute an appropriate tax system with an emphasis on broadening the tax base and in some cases, reviewing upwards the tax rates in order to increase the tax effort as well as ensure optimal contribution of taxation towards economic growth and development.",book:{id:"6008",slug:"taxes-and-taxation-trends",title:"Taxes and Taxation Trends",fullTitle:"Taxes and Taxation Trends"},signatures:"Ojijo Odhiambo and Oluwatosin Olushola",authors:[{id:"203736",title:"Mr.",name:"Ojijo",middleName:null,surname:"Odhiambo",slug:"ojijo-odhiambo",fullName:"Ojijo Odhiambo"},{id:"206483",title:"Mr.",name:"Oluwatosin",middleName:null,surname:"Olushola",slug:"oluwatosin-olushola",fullName:"Oluwatosin Olushola"}]},{id:"74196",doi:"10.5772/intechopen.94919",title:"Meeting the Needs of Fourth Industrial Revolution (4IR) in Entrepreneurial Education in Malaysia: The Government’s Role",slug:"meeting-the-needs-of-fourth-industrial-revolution-4ir-in-entrepreneurial-education-in-malaysia-the-g",totalDownloads:516,totalCrossrefCites:3,totalDimensionsCites:3,abstract:"Entrepreneurship education holds great value for all students of science, technology, mission work, social work, healthcare, and education. It also serves as a great incubator for the types of creative, innovative ideas of our students and the global needs in the 21st century where combining entrepreneurship syllabus and exposure of the fourth industrial revolution is essential. This study explores the Fourth Industrial Revolution (4IR) as an opportunity to change models of innovation-driven entrepreneurship for the better, and create an environment that makes entrepreneurship more inclusive, while maximizing the Fourth Industrial Revolution’s benefits to the society and minimizing the risks that come with it. The role of Malaysian government in enhancing entrepreneurial education must therefore recognize the fourth industrial evolution and its impacts that must be compatible with Malaysia’s industry policy. Promotion of entrepreneurial experimentation within an appropriate entrepreneurial education ecosystem will provide entrepreneurs with smart government support that invests in entrepreneurial skills in Malaysia. This article assesses (i) fourth industrial revolution impact on entrepreneurial education; (ii) new expectations arising from impacts of fourth industrial evolution in Malaysia: method in teaching and learning; (iii) government’s role in supporting entrepreneurship education and finally (iv) entrepreneurial education reforms in Malaysia.",book:{id:"10215",slug:"circular-economy-recent-advances-new-perspectives-and-applications",title:"Circular Economy",fullTitle:"Circular Economy - Recent Advances, New Perspectives and Applications"},signatures:"Hanim Kamaruddin, Rosilah Hassan, Norasmah Othman, Wan Mimi Diyana Wan Zaki and Sarmila Md Sum",authors:[{id:"267217",title:"Dr.",name:"Wan Mimi Diyana Bt",middleName:null,surname:"Zaki",slug:"wan-mimi-diyana-bt-zaki",fullName:"Wan Mimi Diyana Bt Zaki"},{id:"286496",title:"Dr.",name:"Rosilah",middleName:null,surname:"Hassan",slug:"rosilah-hassan",fullName:"Rosilah Hassan"},{id:"323088",title:"Ph.D.",name:"Hanim",middleName:null,surname:"Kamaruddin",slug:"hanim-kamaruddin",fullName:"Hanim Kamaruddin"},{id:"323105",title:"Prof.",name:"Norasmah",middleName:null,surname:"Othman",slug:"norasmah-othman",fullName:"Norasmah Othman"},{id:"323106",title:"Dr.",name:"Sarmila",middleName:null,surname:"Md Sum",slug:"sarmila-md-sum",fullName:"Sarmila Md Sum"}]}],mostDownloadedChaptersLast30Days:[{id:"66110",title:"Gold Recovery Process from Primary and Secondary Resources Using Bioadsorbents",slug:"gold-recovery-process-from-primary-and-secondary-resources-using-bioadsorbents",totalDownloads:2036,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"Bioadsorbents were prepared in a simple manner only by treating in boiling concentrated sulfuric acid from various biomass materials such as various polysaccharides, persimmon tannin, cotton, paper and biomass wastes such as orange juice residue and microalgae residue after extracting biofuel. These bioadsorbents exhibited high selectivity only to gold over other metals and extraordinary high loading capacity for gold(III), which were elucidated to be attributable to the selective reduction of gold(III) ion to elemental gold due to its highest oxidation-reduction potential of gold(III) of metal ions, catalyzed by the surface of bioadsorbents prepared in boiling sulfuric acid. By using these biosorbents, recovery of gold from actual samples of printed circuit boards of spent mobile phones and Mongolian gold ore was investigated. Recovery of trace concentration of gold(I) from simulated spent alkaline cyanide solution was also investigated using the bioadsorbent. Application of bioadsorbents to some recovery processes of gold from cyanide solutions was proposed.",book:{id:"8150",slug:"elements-of-bioeconomy",title:"Elements of Bioeconomy",fullTitle:"Elements of Bioeconomy"},signatures:"Katsutoshi Inoue, Durga Parajuli, Manju Gurung, Bimala Pangeni, Kanjana Khunathai, Keisuke Ohto and Hidetaka Kawakita",authors:[{id:"198951",title:"Prof.",name:"Keisuke",middleName:null,surname:"Ohto",slug:"keisuke-ohto",fullName:"Keisuke Ohto"},{id:"259238",title:"Dr.",name:"Hidetaka",middleName:null,surname:"Kawakita",slug:"hidetaka-kawakita",fullName:"Hidetaka Kawakita"},{id:"289372",title:"Dr.",name:"Katsutoshi",middleName:null,surname:"Inoue",slug:"katsutoshi-inoue",fullName:"Katsutoshi Inoue"},{id:"298633",title:"Dr.",name:"Bimala",middleName:null,surname:"Pangeni",slug:"bimala-pangeni",fullName:"Bimala Pangeni"},{id:"298634",title:"Dr.",name:"Manju",middleName:null,surname:"Gurung",slug:"manju-gurung",fullName:"Manju Gurung"},{id:"298635",title:"Dr.",name:"Kanjana",middleName:null,surname:"Khunathai",slug:"kanjana-khunathai",fullName:"Kanjana Khunathai"},{id:"298636",title:"Dr.",name:"Durga",middleName:null,surname:"Parajuli",slug:"durga-parajuli",fullName:"Durga Parajuli"}]},{id:"59430",title:"Taxation and Economic Growth in a Resource-Rich Country: The Case of Nigeria",slug:"taxation-and-economic-growth-in-a-resource-rich-country-the-case-of-nigeria",totalDownloads:3913,totalCrossrefCites:3,totalDimensionsCites:4,abstract:"In this chapter, we examine the relationship between taxation and economic growth in a resource rich country, using Nigeria as a case study. We explore the linkages between availability of higher resource revenue and lower taxation effort of other revenue categories and the effects of these on growth. Ordinary least square (OLS) estimation technique is employed in estimating the specified model. Also, descriptive analysis is carried out regarding tax trends and tax efforts in Nigeria to determine the effectiveness of existing tax structures, as well to as examine relevant national and cross-country data. Empirical results reveal that taxation has a significant impact on Real GDP growth rates. However, the proportion of tax contribution to the growth rate falls short of the optimal level in terms of the volume of economic activities and value of total output. Nigeria also lags other African countries with respect to tax effort and as such has a huge untapped potential for enhanced revenue mobilisation. We recommend therefore, that the Government should institute an appropriate tax system with an emphasis on broadening the tax base and in some cases, reviewing upwards the tax rates in order to increase the tax effort as well as ensure optimal contribution of taxation towards economic growth and development.",book:{id:"6008",slug:"taxes-and-taxation-trends",title:"Taxes and Taxation Trends",fullTitle:"Taxes and Taxation Trends"},signatures:"Ojijo Odhiambo and Oluwatosin Olushola",authors:[{id:"203736",title:"Mr.",name:"Ojijo",middleName:null,surname:"Odhiambo",slug:"ojijo-odhiambo",fullName:"Ojijo Odhiambo"},{id:"206483",title:"Mr.",name:"Oluwatosin",middleName:null,surname:"Olushola",slug:"oluwatosin-olushola",fullName:"Oluwatosin Olushola"}]},{id:"71401",title:"Budget Deficit and the Federal Government Debt in Malaysia",slug:"budget-deficit-and-the-federal-government-debt-in-malaysia",totalDownloads:1226,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"In general, most countries in the world, particularly developing countries, are facing significant budget constraints, in which the collection of tax and nontax revenues is less than the government’s total expenditure. Therefore, borrowing either from the local capital or international capital markets is made. Borrowing increases government debts. The budget deficits and the growth of the government debt are the major factors that determine the health of macroeconomics. There is a solid consensus among economists mainly on the effect of budget deficits on macroeconomics in terms of crowding out private investment, increasing interest rates, expanding money supply and escalating consumer price and in certain extent affect exchange rate. Government bonds issued to finance budget deficits are also in question as part of the net wealth of private sectors. On the other side, there is an agreement that the budget deficits financed by the issuance of bonds will crowd out private investment through increasing interest rate. This paper plans to investigate the impact of budget deficits on Malaysia’s economy. Cointegration test and vector error correction models are used to examine the impact of budget deficits on certain macroeconomic variables.",book:{id:"9030",slug:"perspectives-on-economic-development-public-policy-culture-and-economic-development",title:"Perspectives on Economic Development",fullTitle:"Perspectives on Economic Development - Public Policy, Culture, and Economic Development"},signatures:"Mohamed Aslam and Raihan Jaafar",authors:null},{id:"56708",title:"Human Development and Research-Development-Extension Relationships",slug:"human-development-and-research-development-extension-relationships",totalDownloads:1774,totalCrossrefCites:1,totalDimensionsCites:5,abstract:"Human capital is the most important strategic factor for development; as new technologies emerge, the market demand for better and healthier products and consumer demand in terms of quality and delivery time are changing. In today’s world, it becomes increasingly important to know how information can be accessed, how it is adopted, and how it can be assimilated. In this respect, each country allocates budget for training, education, and extension according to its own conditions. This budget may be intended for rural community-based social assistance, but the economic and welfare effect is essential. In this way, it is aimed to increase the living standards of the families living in the rural areas. This will naturally contribute to national income and to the prosperity of society. The subject has been discussed generally in the world, especially in the case of Turkey. According to this, all over the world, particularly in developing countries, research and extension (R&E) is very important and should be considered at least as much as research and development (R&D). However, it will be ensured that societies meet with the technology produced. For this, the development of human resources should be emphasized and a suitable atmosphere should be prepared for this widespread prosperity.",book:{id:"5819",slug:"research-and-development-evolving-trends-and-practices-towards-human-institutional-and-economic-sectors-growth",title:"Research and Development Evolving Trends and Practices",fullTitle:"Research and Development Evolving Trends and Practices - Towards Human, Institutional and Economic Sectors Growth"},signatures:"Orhan Özçatalbaş",authors:[{id:"170206",title:"Prof.",name:"Dr. Orhan",middleName:null,surname:"Özçatalbaş",slug:"dr.-orhan-ozcatalbas",fullName:"Dr. Orhan Özçatalbaş"}]},{id:"68851",title:"Introductory Chapter: Objectives and Scope of Bioeconomy",slug:"introductory-chapter-objectives-and-scope-of-bioeconomy",totalDownloads:996,totalCrossrefCites:0,totalDimensionsCites:0,abstract:null,book:{id:"8150",slug:"elements-of-bioeconomy",title:"Elements of Bioeconomy",fullTitle:"Elements of Bioeconomy"},signatures:"Krzysztof Biernat",authors:[{id:"155009",title:"Prof.",name:"Krzysztof",middleName:null,surname:"Biernat",slug:"krzysztof-biernat",fullName:"Krzysztof Biernat"}]}],onlineFirstChaptersFilter:{topicId:"66",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:139,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:123,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:21,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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",coverUrl:"https://cdn.intechopen.com/series/covers/3.jpg",latestPublicationDate:"August 4th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:9,editor:{id:"419588",title:"Ph.D.",name:"Sergio",middleName:"Alexandre",surname:"Gehrke",slug:"sergio-gehrke",fullName:"Sergio Gehrke",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038WgMKQA0/Profile_Picture_2022-06-02T11:44:20.jpg",biography:"Dr. Sergio Alexandre Gehrke is a doctorate holder in two fields. The first is a Ph.D. in Cellular and Molecular Biology from the Pontificia Catholic University, Porto Alegre, Brazil, in 2010 and the other is an International Ph.D. in Bioengineering from the Universidad Miguel Hernandez, Elche/Alicante, Spain, obtained in 2020. In 2018, he completed a postdoctoral fellowship in Materials Engineering in the NUCLEMAT of the Pontificia Catholic University, Porto Alegre, Brazil. He is currently the Director of the Postgraduate Program in Implantology of the Bioface/UCAM/PgO (Montevideo, Uruguay), Director of the Cathedra of Biotechnology of the Catholic University of Murcia (Murcia, Spain), an Extraordinary Full Professor of the Catholic University of Murcia (Murcia, Spain) as well as the Director of the private center of research Biotecnos – Technology and Science (Montevideo, Uruguay). Applied biomaterials, cellular and molecular biology, and dental implants are among his research interests. He has published several original papers in renowned journals. In addition, he is also a Collaborating Professor in several Postgraduate programs at different universities all over the world.",institutionString:null,institution:{name:"Universidad Católica San Antonio de Murcia",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:2,paginationItems:[{id:"1",title:"Oral Health",coverUrl:"https://cdn.intechopen.com/series_topics/covers/1.jpg",isOpenForSubmission:!0,editor:{id:"173955",title:"Prof.",name:"Sandra",middleName:null,surname:"Marinho",slug:"sandra-marinho",fullName:"Sandra Marinho",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRGYMQA4/Profile_Picture_2022-06-01T13:22:41.png",biography:"Dr. Sandra A. Marinho is an Associate Professor and Brazilian researcher at the State University of Paraíba (Universidade Estadual da Paraíba- UEPB), Campus VIII, located in Araruna, state of Paraíba since 2011. She holds a degree in Dentistry from the Federal University of Alfenas (UNIFAL), while her specialization and professional improvement in Stomatology took place at Hospital Heliopolis (São Paulo, SP). Her qualifications are: a specialist in Dental Imaging and Radiology, Master in Dentistry (Periodontics) from the University of São Paulo (FORP-USP, Ribeirão Preto, SP), and Doctor (Ph.D.) in Dentistry (Stomatology Clinic) from Hospital São Lucas of the Pontifical Catholic University of Rio Grande do Sul (HSL-PUCRS, Porto Alegre, RS). She held a postdoctoral internship at the Federal University from Jequitinhonha and Mucuri Valleys (UFVJM, Diamantina, MG). She is currently a member of the Brazilian Society for Dental Research (SBPqO) and the Brazilian Society of Stomatology and Pathology (SOBEP). Dr. Marinho's experience in Dentistry mainly covers the following subjects: oral diagnosis, oral radiology; oral medicine; lesions and oral infections; oral pathology, laser therapy and epidemiological studies.",institutionString:null,institution:{name:"State University of Paraíba",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null},{id:"2",title:"Prosthodontics and Implant Dentistry",coverUrl:"https://cdn.intechopen.com/series_topics/covers/2.jpg",isOpenForSubmission:!0,editor:{id:"179568",title:"Associate Prof.",name:"Wen Lin",middleName:null,surname:"Chai",slug:"wen-lin-chai",fullName:"Wen Lin Chai",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRHGAQA4/Profile_Picture_2022-05-23T14:31:12.png",biography:"Professor Dr. Chai Wen Lin is currently a lecturer at the Department of Restorative Dentistry, Faculty of Dentistry of the University of Malaya. She obtained a Master of Dental Science in 2006 and a Ph.D. in 2011. Her Ph.D. research work on the soft tissue-implant interface at the University of Sheffield has yielded several important publications in the key implant journals. She was awarded an Excellent Exchange Award by the University of Sheffield which gave her the opportunity to work at the famous Faculty of Dentistry of the University of Gothenburg, Sweden, under the tutelage of Prof. Peter Thomsen. In 2016, she was appointed as a visiting scholar at UCLA, USA, with attachment in Hospital Dentistry, and involvement in research work related to zirconia implant. In 2016, her contribution to dentistry was recognized by the Royal College of Surgeon of Edinburgh with her being awarded a Fellowship in Dental Surgery. She has authored numerous papers published both in local and international journals. She was the Editor of the Malaysian Dental Journal for several years. Her main research interests are implant-soft tissue interface, zirconia implant, photofunctionalization, 3D-oral mucosal model and pulpal regeneration.",institutionString:null,institution:{name:"University of Malaya",institutionURL:null,country:{name:"Malaysia"}}},editorTwo:{id:"479686",title:"Dr.",name:"Ghee Seong",middleName:null,surname:"Lim",slug:"ghee-seong-lim",fullName:"Ghee Seong Lim",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003ScjLZQAZ/Profile_Picture_2022-06-08T14:17:06.png",biography:"Assoc. Prof Dr. Lim Ghee Seong graduated with a Bachelor of Dental Surgery from University of Malaya, Kuala Lumpur in 2008. He then pursued his Master in Clinical Dentistry, specializing in Restorative Dentistry at Newcastle University, Newcastle, UK, where he graduated with distinction. He has also been awarded the International Training Fellowship (Restorative Dentistry) from the Royal College of Surgeons. His passion for teaching then led him to join the faculty of dentistry at University Malaya and he has since became a valuable lecturer and clinical specialist in the Department of Restorative Dentistry. He is currently the removable prosthodontic undergraduate year 3 coordinator, head of the undergraduate module on occlusion and a member of the multidisciplinary team for the TMD clinic. He has previous membership in the British Society for Restorative Dentistry, the Malaysian Association of Aesthetic Dentistry and he is currently a lifetime member of the Malaysian Association for Prosthodontics. Currently, he is also the examiner for the Restorative Specialty Membership Examinations, Royal College of Surgeons, England. He has authored and co-authored handful of both local and international journal articles. 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