Leisheng Zhang

By Leisheng Zhang and Zhihai Han

Hydrogels are splendid biomaterials and play a critical role in multiple applications for disease management via offering a microenvironment for drug metabolism and exerting the bonding effect attribute to the preferable physical and chemical properties. State-of-the-art renewal has indicated the combination of hydrogels with mesenchymal stem/stromal cells (MSCs), which are heterogeneous populations with unique hematopoietic-supporting and immunoregulatory properties. For decades, we and other investigators have demonstrated the promising prospects of MSCs in regenerative medicine, and in particular, for the administration of recurrent and refractory disease. Very recently, we took advantage of the hydrogel/MSC composite for the applications in osteoarthritis, burn wounds, and refractory wounds associated with diabetic foot as well. Strikingly, the composite showed superiority in continuous improvement of the biological functions of the injured areas over hydrogels or MSCs, respectively. Collectively, hydrogel-based biomaterials are of importance for disease treatment and the accompanied regenerative medicine. Therefore, in this chapter, we will summarize the latest updates of hydrogel/MSCs composite in tissue engineering and put forward the direction of hotspot issues in the future including hydrogel/MSC and hydrogel/MSC-exosome in preclinical and clinical studies.

Part of the book: Hydrogels

By Leisheng Zhang and Hui Cai

Immunotherapies are revolutionizing strategies for cancer treatment and infectious disease administration, which thus occupy worldwide concerns and enthusiasms for conquering relapsing and refractory immunodysfuction-related diseases. Current preclinical and clinical studies have suggested the partial success and promising potential of cancer management by various immunotherapies such as cancer vaccine, lymphocyte-promoting cytokines, checkpoint inhibitors and the cellular immunotherapy. However, the precise controlled modulation of the recipient’s immune system as well as the concomitant cytotoxicity remains the core challenge in the broad implementation of cancer immunotherapies. In this Chapter, we mainly focus on the latest updates of the cytotoxicity of cancer immunocytotherapy, together with the remarkable opportunities and conspicuous challenges, which represent the paradigm for boosting the immune system to enhance antitumor responses and ultimately eliminate malignancies. Collectively, we summarize and highlight the auspicious improvement in the efficacy and cytotoxicity of cancer immunotherapy and will benefit the large-scale preclinical investigations and clinical practice in adoptive immunotherapy.

Part of the book: Cytotoxicity

By Hao Yu, Zhihai Han, Cunrong Chen and Leisheng Zhang

Cancers including hematological malignancies and metastatic solid tumors are one of the life-threatening diseases to the general population, which have become a heavy burden for patients and their caregivers physically and mentally. Despite the great progression in preclinical and clinical studies, effective implementation strategies are urgently needed to optimize the advancements in cancer diagnosis and treatment. State-of-the-art updates have indicated the application of multifunctional nanotheranostics as an emerging diagnostic and therapeutic tool for cancer management. Herein, this chapter displayed the literature and description of various nanomaterial-based noninvasive diagnostic and therapeutic approaches for cancer administration from the view of nanomaterial classification and nanomaterial-based application in nanotheranostics as well as the promising perspectives and grand challenges in nanomedicine. Collectively, this review will provide overwhelming new references for cancer supervision and benefit the medical and pharmaceutical practice in the field of nanotheranostics.

Part of the book: Biotechnology

By Leisheng Zhang, Zhongchao Han and Xiaowei Gao

Allergic diseases are a clump of disorders caused by protective or harmful immune responses to specific exogenous stimulations. To date, the worldwide prevalence of allergic diseases has caused considerable perplex to patients and guardians physically and mentally. Despite the significant advances in preclinical investigation and clinical practice, yet the effective treatment strategies for allergic diseases are far from satisfaction. State-of-the-art renewal has highlighted the involvement of mesenchymal stem/stromal cell (MSC)-based cytotherapy for various allergic disease management including atopic dermatitis, pediatric asthma, allergic rhinitis, and urticaria, which largely attributes to the unique immunomodulatory properties and mode of action via autocrine and paracrine, direct- or trans-differentiation. In this chapter, we mainly focus on the latest updates of MSC-based investigations upon allergic disease administration as well as the concomitant prospective and challenges, which will provide overwhelming new references for MSC-based cytotherapy in regenerative medicine.

Part of the book: Allergic Disease

By Leisheng Zhang, Zhihai Han, Zhongchao Han and Hui Cai

Osteoarthritis (OA), a principal and challenging disorder of articular cartilage, has been regarded as the most frequent and prevalent chronic disease of degenerative joints, which is caused by multiple factors including aging, trauma, overweight, joint deformity and congenital abnormality, together with the increase in life expectancy. In spite of considerable improvements that have been obtained by conducting multidisciplinary therapies such as surgical procedures and anti-inflammatory drugs, the pathogenesis and efficacy of OA with functional losses and degeneration are still elusively complicated for ascertainment. Mesenchymal stem/stromal cells (MSCs), also termed as multipotent mesenchymal progenitor/precursor cells, skeletal stem cells, or medicinal signaling cells, are heterogeneous cell populations with hematopoietic-supporting and immunomodulatory properties, together with multilineage differentiation property. For decades, investigators have illuminated the application of the advantaged and promising sources with/without remarkable biomaterials for the treatment of recurrent and refractory disorders including OA. In this chapter, we mainly concentrate on the current progress of MSC-based cytotherapy in both preclinical study and clinical practice as well as the promising prospective and critical challenges in the field, which will conformably benefit the administration of OA in future.

Part of the book: Arthroplasty

By Baoquan Song and Leisheng Zhang

Ferroptosis is a newly defined programmed cell death (PCD) process with the hallmark of the accumulation of iron-dependent lipid peroxidation, which is more immunogenic over apoptosis. Ferroptosis shows great potential as a therapeutic target against acute kidney injury (AKI), cancers, cardiovascular diseases, neurodegenerative diseases, and hepatic diseases. Accumulating evidence has highlighted that ferroptosis plays an unneglectable role in regulating the development and progression of multiple pathologies of leukemia including acute myeloid leukemia (AML), chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), and chronic lymphocytic leukemia (CLL). Herein, we focus on the state-of-the-art renewal in the relationship of ferroptosis with leukemia. Meanwhile, this chapter further highlights the iron, lipid and amino acid metabolism, as well as ferroptosis-based molecular mechanisms. Collectively, we summarize the contribution of ferroptosis to the pathogenesis of leukemia and discuss ferroptosis as a novel therapeutic target for different types of leukemia.

Part of the book: Cell Death and Disease

By Leisheng Zhang, Xiaoming Feng, Zhihai Han and Zhongchao Han

Natural killer (NK) cells are advantaged immune cells and play a pivotal role in both innate and adaptive immune responses. To date, autogenous and allogenic NK cells have been generated from a variety of origins, including perinatal blood (e.g., umbilical cord blood and placental blood), peripheral blood, and even stem cells (hematopoietic stem cells and pluripotent stem cells). NK cells function mainly via antibody-dependent cell-mediated cytotoxicity (ADCC), direct cytolytic effect, and paracrine effects (e.g., IFN-γ, GM-CSF, granzyme, and perforin). Distinguishing from the adaptive immunizing cells (e.g., T and B lymphocytes), NK cells, and chimeric antigen receptor-transduced NK (CAR-NK), cell-based cytotherapy is adequate to fulfill the biofunction of eliminating pathogenic infection, combating hematological malignancies and metastatic solid tumors, and delaying aging. In this chapter, we mainly focus on the state-of-the-art renewal of NK cell-based cytotherapy for cancer immunosurveillance and immunotherapy from the view of high-efficient in vitro preparation (e.g., candidate cell sources and ex vivo cultivation) and preclinical and clinical investigation. Furthermore, we also figure out the promising prospects and the concomitant challenges of NK cell-based remedies for cancer management in future, which will collectively benefit the development of NK cell-based cancer immunotherapy in future.

Part of the book: Natural Killer Cells

By Shixun Ma, Li Li, Jintang Yin, Xiaohu Wang, Chongya Yang, Leisheng Zhang, Tiankang Guo and Hui Cai

Gastric cancer is one of the common malignant tumors in the gastrointestinal tract, and the treatment of gastric cancer includes the main ways such as radical resection, adjuvant chemotherapy, palliative care, and drug therapy; however, patients often have defects such as high recurrence rate, high treatment burden, and serious side effects, which impose a heavy burden on the economic and social construction and patients’ families. In recent years, novel gastric cancer treatment methods featuring tumor immunotherapy have provided new treatment strategies to improve the above-mentioned defects and increase the cure rate of patients. Natural killer cells (NK cells) are key components of the body’s intrinsic immune response and can participate in both the intrinsic and adaptive immune responses, exercising the functions of tumor killing, removing pathogenic microorganisms or abnormal cells and enhancing immunity, and thus have broad prospects for new drug development and clinical treatment. This article reviews the biological properties and functions of NK cells and their interrelationship with gastric cancer treatment, and provides a reference for clinical research.

Part of the book: Natural Killer Cells

By Leisheng Zhang, Xiaowei Gao, Shixun Ma, Miao Yu, Xianghong Xu, Yuanguang Zhao, Shuang Chen, Yonghong Li, Xiaonan Yang, Tiankang Guo and Hui Cai

Mesenchymal stem cells (MSCs), also known as mesenchymal stromal cells or medicinal signaling cells or multipotent stem cells, are heterogeneous cell populations with unique immunomodulatory feature and hematopoietic-supporting capacity. MSCs function through a variety of approaches including paracrine and autocrine, direct- or trans-differentiation, bidirectional immunomodulation, and serving as constitutive microenvironment. Of them, exosomes and microvesicles function as the pivotal vehicle for mediating the ameliorative and therapeutic effect of MSCs toward various recurrent and refractory diseases, such as xerophthalmia, radioactive nasal mucosa injury, acute-on-chronic liver failure (ACLF), dermal chronic ulcers, and intrauterine adhesions. State-of-the-art renewal has also highlighted the promising prospective of MSC-derived exosomes (MSC-exo) and diverse biomaterial composites in regenerative medicine. In this book chapter, we mainly focus on the concept, biological phenotypes, preclinical research, and clinical practice of MSC-derived exosomes (MSC-Exos) and/or biomaterials, which will collectively supply overwhelming new references for the further development of MSC-Exos-based biotherapy and disease diagnosis in future.

Part of the book: Exosomes

By Hao Yu, Xiaonan Yang, Shuang Chen, Xianghong Xu, Zhihai Han, Hui Cai, Zheng Guan and Leisheng Zhang

Mesenchymal stem/stromal cells (MSCs) with hematopoietic-supporting and immunoregulatory properties have aroused great expectations in the field of regenerative medicine and the concomitant pathogenesis. However, many obstacles still remain before the large-scale preparation of homogeneous and standardized MSCs with high cellular vitality for clinical purposes ascribe to elusive nature and biofunction of MSCs derived from various adult and fetal sources. Current progress in human pluripotent stem cells (hPSCs), including embryonic stem cells (ESCs) and induced PSCs (iPSCs), have highlighted the feasibility of MSC development and disease remodeling, together with robust MSC generation dispense from the inherent disadvantages of the aforementioned MSCs including ethical and pathogenic risks, donor heterogeneity and invasiveness. Herein, we review the state-of-the-art updates of advances for MSC preparation from hPSCs and multiple tissues (perinatal tissue, adult tissue) as well as tumor intervention with biomaterials, and thus propose a framework for MSCs-based oncotherapy in regenerative medicine. Collectively, we describe the landscape of in vitro generation and functional hierarchical organization of hPSC-MSCs, which will supply overwhelming new references for further dissecting MSC-based tissue engineering and disease remodeling.

Part of the book: Advances in Pluripotent Stem Cells