Mesenchymal Stem Cells in Human Health and Diseases

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Author :
Publisher : Academic Press
ISBN 13 : 0128205334
Total Pages : 230 pages
Book Rating : 4.1/5 (282 download)

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Book Synopsis Mesenchymal Stem Cells in Human Health and Diseases by : Ahmed El-Hashash

Download or read book Mesenchymal Stem Cells in Human Health and Diseases written by Ahmed El-Hashash and published by Academic Press. This book was released on 2020-01-07 with total page 230 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mesenchymal Stem Cells in Human Health and Diseases provides a contemporary overview of the fast-moving field of MSC biology, regenerative medicine and therapeutics. MSCs offer the potential to dramatically reduce human suffering from disease. Numerous MSC-based studies are ongoing each year, each offering hope for novel treatments in human disease. This book provides information on MSC application in well-studied human diseases and tissue repair/regeneration and recent advances in their research and treatment. These discoveries are placed within the structural context of tissue and developmental biology in sections dealing with recent advances in our understanding of MSC biology. Includes insights ranging from MSC biology and development through the derivation and identification and properties of MSCs Helps to identify potential innovative solutions for restoring normal morphogenesis and/or regeneration of diseased organs Discusses the fact-based promise of MSC therapeutics and regenerative medicine in the real world

Mesenchymal Stem Cell Therapy

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Publisher : Springer Science & Business Media
ISBN 13 : 1627032002
Total Pages : 458 pages
Book Rating : 4.6/5 (27 download)

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Book Synopsis Mesenchymal Stem Cell Therapy by : Lucas G. Chase

Download or read book Mesenchymal Stem Cell Therapy written by Lucas G. Chase and published by Springer Science & Business Media. This book was released on 2012-12-12 with total page 458 pages. Available in PDF, EPUB and Kindle. Book excerpt: Over the past decade, significant efforts have been made to develop stem cell-based therapies for difficult to treat diseases. Multipotent mesenchymal stromal cells, also referred to as mesenchymal stem cells (MSCs), appear to hold great promise in regards to a regenerative cell-based therapy for the treatment of these diseases. Currently, more than 200 clinical trials are underway worldwide exploring the use of MSCs for the treatment of a wide range of disorders including bone, cartilage and tendon damage, myocardial infarction, graft-versus-host disease, Crohn’s disease, diabetes, multiple sclerosis, critical limb ischemia and many others. MSCs were first identified by Friendenstein and colleagues as an adherent stromal cell population within the bone marrow with the ability to form clonogenic colonies in vitro. In regards to the basic biology associated with MSCs, there has been tremendous progress towards understanding this cell population’s phenotype and function from a range of tissue sources. Despite enormous progress and an overall increased understanding of MSCs at the molecular and cellular level, several critical questions remain to be answered in regards to the use of these cells in therapeutic applications. Clinically, both autologous and allogenic approaches for the transplantation of MSCs are being explored. Several of the processing steps needed for the clinical application of MSCs, including isolation from various tissues, scalable in vitro expansion, cell banking, dose preparation, quality control parameters, delivery methods and numerous others are being extensively studied. Despite a significant number of ongoing clinical trials, none of the current therapeutic approaches have, at this point, become a standard of care treatment. Although exceptionally promising, the clinical translation of MSC-based therapies is still a work in progress. The extensive number of ongoing clinical trials is expected to provide a clearer path forward for the realization and implementation of MSCs in regenerative medicine. Towards this end, reviews of current clinical trial results and discussions of relevant topics association with the clinical application of MSCs are compiled in this book from some of the leading researchers in this exciting and rapidly advancing field. Although not absolutely all-inclusive, we hope the chapters within this book can promote and enable a better understanding of the translation of MSCs from bench-to-bedside and inspire researchers to further explore this promising and quickly evolving field.

Mesenchymal Stem Cell Assays and Applications

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Publisher : Humana Press
ISBN 13 : 9781493957798
Total Pages : 534 pages
Book Rating : 4.9/5 (577 download)

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Book Synopsis Mesenchymal Stem Cell Assays and Applications by : Mohan C Vemuri

Download or read book Mesenchymal Stem Cell Assays and Applications written by Mohan C Vemuri and published by Humana Press. This book was released on 2017-05-04 with total page 534 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mesenchymal Stem Cells have seen an unprecedented level of interest in the last decade, primarily due to their relative ease of isolation, the large numbers of cells present in the adult, and the ability to propagate these cells in culture. In Mesenchymal Stem Cell Assays and Applications, expert researchers from across the globe explore the latest techniques to propagate, characterize, and engineer this special cell type. Chapters outline a set of protocols and assays used by leading investigators in the field, providing standards that can be applied by all researchers to the population of cells used in their experiments. Composed in the highly successful Methods in Molecular BiologyTM series format, each chapter contains a brief introduction, step-by-step methods, a list of necessary materials, and a Notes section which shares tips on troubleshooting and avoiding known pitfalls. Ground-breaking and current, Mesenchymal Stem Cell Assays and Applications is a necessary handbook for all researchers working with this ambiguous population of cells.

Mesenchymal Stem Cells - Basics and Clinical Application II

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Publisher : Springer
ISBN 13 : 3642379443
Total Pages : 309 pages
Book Rating : 4.6/5 (423 download)

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Book Synopsis Mesenchymal Stem Cells - Basics and Clinical Application II by : Birgit Weyand

Download or read book Mesenchymal Stem Cells - Basics and Clinical Application II written by Birgit Weyand and published by Springer. This book was released on 2014-07-08 with total page 309 pages. Available in PDF, EPUB and Kindle. Book excerpt: Engineered MSCs from Patient-Specific iPS Cells, by Irina Eberle, Mohsen Moslem, Reinhard Henschler, Tobias Cantz Fate of Intravenously Injected Mesenchymal Stem Cells and Significance for Clinical Application, by Beate Wagner, Reinhard Henschler The Implications of Stem Cell Applications for Diseases of the Respiratory System, by Mei Ling Lim, Philipp Jungebluth, Paolo Macchiarini Potential of Mesenchymal Stem Cell Applications in Plastic and Reconstructive Surgery, by Birgit Weyand, Peter M. Vogt General Principles for the Regeneration of Bone and Cartilage, by Michael Jagodzinski, C. Haasper Adult Mesenchymal Stem Cells Explored in the Dental Field, by K. M. Fawzy El-Sayed, C. Dörfer, F. Fändrich, F. Gieseler, M. H. Moustafa, H. Ungefroren Mesenchymal Stem Cell Therapy and Lung Diseases, by Khondoker M. Akram, Sohel Samad, Monica Spiteri, Nicholas R. Forsyth Mesenchymal Stem Cells as Cellular Immunotherapeutics in Allogeneic Hematopoietic Stem Cell Transplantation, by Claudia Papewalis, Daniela Topolar, Barbara Götz, Stefan Schönberger, Dagmar Dilloo New Cell-Based Therapy Paradigm: Induction of Bone Marrow-Derived Multipotent Mesenchymal Stromal Cells into Pro-Inflammatory MSC1 and Anti-inflammatory MSC2 Phenotypes, by Aline M. Betancourt Interactions Between Mesenchymal Stem Cells and Dendritic Cells, by Grazia Maria Spaggiari, Lorenzo Moretta MSC and Tumors: Homing, Differentiation, and Secretion Influence Therapeutic Potential, by Naomi D’souza, Jorge Sans Burns, Giulia Grisendi, Olivia Candini, Elena Veronesi, Serena Piccinno, Edwin M. Horwitz, Paolo Paolucci, Pierfranco Conte, Massimo Dominici Sources of Mesenchymal Stem Cells: Current and Future Clinical Use, by Michela Pozzobon, Martina Piccoli, Paolo De Coppi Role of the EU Framework in Regulation of Stem Cell-Based Products, by Giovanni Migliaccio, Cristina Pintus

Mesenchymal Stem Cell in Veterinary Sciences

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Author :
Publisher : Springer Nature
ISBN 13 : 9811560374
Total Pages : 347 pages
Book Rating : 4.8/5 (115 download)

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Book Synopsis Mesenchymal Stem Cell in Veterinary Sciences by : Mudasir Bashir Gugjoo

Download or read book Mesenchymal Stem Cell in Veterinary Sciences written by Mudasir Bashir Gugjoo and published by Springer Nature. This book was released on 2020-11-09 with total page 347 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book focuses on mesenchymal stem cells (MSCs) of animal origin, including their isolation, characterization, and clinical applications. After briefly discussing the historical development of the field of stem cell research, it describes the basic properties and nature of stem cells particularly in relation to MSCs. In turn, it reviews materials and methods used to isolate MSCs from various sources, culture expansion, characterization and long-term storage. It also explores the therapeutic efficacy, immunomodulation and anti-inflammatory, and differentiation properties of MSCs. Importantly, the book discusses the applications of genetic engineering to enhance the efficacy and potential of MSCs in regenerative medicine. The book largely addresses the potential applications of mesenchymal stem cells in therapies for important species of domesticated animals including sheep, goats, cattle, buffalo, cats, dogs and horses. Finally, the book presents an abridgement of challenges and future prospects of stem cell research and application in medicine, in general and veterinary sciences, in particular.

Mesenchymal Stem Cells in Human Health and Diseases

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Author :
Publisher : Academic Press
ISBN 13 : 0128197137
Total Pages : 228 pages
Book Rating : 4.1/5 (281 download)

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Book Synopsis Mesenchymal Stem Cells in Human Health and Diseases by : Ahmed El-Hashash

Download or read book Mesenchymal Stem Cells in Human Health and Diseases written by Ahmed El-Hashash and published by Academic Press. This book was released on 2020-01-06 with total page 228 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mesenchymal Stem Cells in Human Health and Diseases provides a contemporary overview of the fast-moving field of MSC biology, regenerative medicine and therapeutics. MSCs offer the potential to dramatically reduce human suffering from disease. Numerous MSC-based studies are ongoing each year, each offering hope for novel treatments in human disease. This book provides information on MSC application in well-studied human diseases and tissue repair/regeneration and recent advances in their research and treatment. These discoveries are placed within the structural context of tissue and developmental biology in sections dealing with recent advances in our understanding of MSC biology. Includes insights ranging from MSC biology and development through the derivation and identification and properties of MSCs Helps to identify potential innovative solutions for restoring normal morphogenesis and/or regeneration of diseased organs Discusses the fact-based promise of MSC therapeutics and regenerative medicine in the real world

Culture of Cells for Tissue Engineering

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Author :
Publisher : John Wiley & Sons
ISBN 13 : 0471741809
Total Pages : 528 pages
Book Rating : 4.4/5 (717 download)

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Book Synopsis Culture of Cells for Tissue Engineering by : Gordana Vunjak-Novakovic

Download or read book Culture of Cells for Tissue Engineering written by Gordana Vunjak-Novakovic and published by John Wiley & Sons. This book was released on 2006-03-31 with total page 528 pages. Available in PDF, EPUB and Kindle. Book excerpt: Step-by-step, practical guidance for the acquisition, manipulation,and use of cell sources for tissue engineering Tissue engineering is a multidisciplinary field incorporatingthe principles of biology, chemistry, engineering, and medicine tocreate biological substitutes of native tissues for scientificresearch or clinical use. Specific applications of this technologyinclude studies of tissue development and function, investigatingdrug response, and tissue repair and replacement. This area israpidly becoming one of the most promising treatment options forpatients suffering from tissue failure. Written by leading experts in the field, Culture of Cellsfor Tissue Engineering offers step-by-step, practicalguidance for the acquisition, manipulation, and use of cell sourcesfor tissue engineering. It offers a unique focus on tissueengineering methods for cell sourcing and utilization, combiningtheoretical overviews and detailed procedures. Features of the text include: Easy-to-use format with a two-part organization Logically organized—part one discusses cell sourcing,preparation, and characterization and the second part examinesspecific engineered tissues Each chapter covers: structural and functional properties oftissues, methodological principles, culture, cellselection/expansion, cell modifications, cell seeding, tissueculture, analytical assays, and a detailed description ofrepresentative studies End-of-chapter features include useful listings of sources forreagents, materials, and supplies, with the contact details of thesuppliers listed at the end of the book A section of elegant color plates to back up the figures in thechapters Culture of Cells for Tissue Engineering givesnovice and seasoned researchers in tissue engineering an invaluableresource. In addition, the text is suitable for professionals inrelated research, particularly in those areas where cell and tissueculture is a new or emerging tool.

Mesenchymal Stem Cell Derived Exosomes

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Publisher : Academic Press
ISBN 13 : 0128004975
Total Pages : 288 pages
Book Rating : 4.1/5 (28 download)

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Book Synopsis Mesenchymal Stem Cell Derived Exosomes by : Yaoliang Tang

Download or read book Mesenchymal Stem Cell Derived Exosomes written by Yaoliang Tang and published by Academic Press. This book was released on 2015-09-02 with total page 288 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mesenchymal stem cell-derived exosomes are at the forefront of research in two of the most high profile and funded scientific areas – cardiovascular research and stem cells. Mesenchymal Stem Cell Derived Exosomes provides insight into the biofunction and molecular mechanisms, practical tools for research, and a look toward the clinical applications of this exciting phenomenon which is emerging as an effective diagnostic. Primarily focused on the cardiovascular applications where there have been the greatest advancements toward the clinic, this is the first compendium for clinical and biomedical researchers who are interested in integrating MSC-derived exosomes as a diagnostic and therapeutic tool. Introduces the MSC-exosome mediated cell-cell communication Covers the major functional benefits in current MSC-derived exosome studies Discusses strategies for the use of MSC-derived exosomes in cardiovascular therapies

Mesenchymal Stem Cells

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Author :
Publisher : Humana Press
ISBN 13 : 9781588297716
Total Pages : 0 pages
Book Rating : 4.2/5 (977 download)

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Book Synopsis Mesenchymal Stem Cells by : Darwin J. Prockop

Download or read book Mesenchymal Stem Cells written by Darwin J. Prockop and published by Humana Press. This book was released on 2008-03-07 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: For over forty years, mesenchymal stem cells (MSCs) have been scrutinized and studied, garnering much attention due to their broad therapeutic efficacy. In this essential book, leaders in the field were assembled to contribute detailed methodologies for the isolation and characterization of human and rodent MSCs. Cutting edge and easy to use, this book is the perfect resource for scientists attempting to pursue this important and ever-developing field of research.

Progenitor and Stem Cell Technologies and Therapies

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Publisher : Elsevier
ISBN 13 : 0857096079
Total Pages : 568 pages
Book Rating : 4.8/5 (57 download)

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Book Synopsis Progenitor and Stem Cell Technologies and Therapies by : Anthony Atala

Download or read book Progenitor and Stem Cell Technologies and Therapies written by Anthony Atala and published by Elsevier. This book was released on 2012-03-15 with total page 568 pages. Available in PDF, EPUB and Kindle. Book excerpt: Progenitor and stem cells have the ability to renew themselves and change into a variety of specialised types, making them ideal materials for therapy and regenerative medicine. Progenitor and stem cell technologies and therapies reviews the range of progenitor and stem cells available and their therapeutic application. Part one reviews basic principles for the culture of stem cells before discussing technologies for particular cell types. These include human embryonic, induced pluripotent, amniotic and placental, cord and multipotent stem cells. Part two discusses wider issues such as intellectual property, regulation and commercialisation of stem cell technologies and therapies. The final part of the book considers the therapeutic use of stem and progenitor cells. Chapters review the use of adipose tissue-derived stem cells, umbilical cord blood (UCB) stem cells, bone marrow, auditory and oral cavity stem cells. Other chapters cover the use of stem cells in therapies in various clinical areas, including lung, cartilage, urologic, nerve and cardiac repair. With its distinguished editor and international team of contributors, Progenitor and stem cell technologies and therapies is a standard reference for both those researching in cell and tissue biology and engineering as well as medical practitioners investigating the therapeutic use of this important technology. Reviews the range of progenitor and stem cells available and outlines their therapeutic application Examines the basic principles for the culture of stem cells before discussing technologies for particular cell types, including human embryonic, induced pluripotent, amniotic and placental, cord and multipotent stem cells Includes a discussion of wider issues such as intellectual property, regulation and commercialisation of stem cell technologies and therapies

Mesenchymal Stem Cells

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Publisher : Elsevier
ISBN 13 : 0323958494
Total Pages : 158 pages
Book Rating : 4.3/5 (239 download)

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Book Synopsis Mesenchymal Stem Cells by : Leisheng Zhang

Download or read book Mesenchymal Stem Cells written by Leisheng Zhang and published by Elsevier. This book was released on 2023-05-12 with total page 158 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mesenchymal Stem Cells: Biological Concepts, Current Advances, Opportunities and Challenges systematically summarizes and discusses the basic concepts and latest updates of mesenchymal stem cells (MSCs) in the past 60 years, as well as the latest progress of clinical translational research and regulatory policy at home and abroad, which will be of great practical significance for promoting and guiding the future development of stem cell production and regenerative medicine. Systematically introduces the latest updates on Mesenchymal stem cells (MSCs), helping readers have a systematic understanding of MSCs Summarizes knowledge on MSC-based cytotherapy in clinical practice to benefit clinicians and help them design MSC-relevant clinical trials Introduces newly developed concepts of MSC-based tissue engineering

Mesenchymal Stem Cells

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Publisher : BoD – Books on Demand
ISBN 13 : 9535136151
Total Pages : 302 pages
Book Rating : 4.5/5 (351 download)

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Book Synopsis Mesenchymal Stem Cells by : Phuc Van Pham

Download or read book Mesenchymal Stem Cells written by Phuc Van Pham and published by BoD – Books on Demand. This book was released on 2017-11-29 with total page 302 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mesenchymal Stem Cells: Isolation, Characterization, and Applications thoroughly presents the isolation, characterization, and some applications of mesenchymal stem cells in the clinic. The book has two parts: "Isolation and Characterization" and "Clinical Perspectives and Applications." In Part I, the subsequent chapters introduce some techniques in isolation, characterization, and purification of mesenchymal stem cells in different tissues. In Part II, some applications of mesenchymal stem cells in the popular diseases, which include cartilage regeneration, spinal cord injury, and osteoarthritis, are discussed. This book provides a succinct yet comprehensive overview of mesenchymal stem cells for advanced students, graduate students, and researchers.

Mesenchymal Stem Cells and Skeletal Regeneration

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Publisher : Academic Press
ISBN 13 : 9780124079151
Total Pages : 0 pages
Book Rating : 4.0/5 (791 download)

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Book Synopsis Mesenchymal Stem Cells and Skeletal Regeneration by : Peter Giannoudis

Download or read book Mesenchymal Stem Cells and Skeletal Regeneration written by Peter Giannoudis and published by Academic Press. This book was released on 2013-03-18 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book covers our current understanding of the role of mesenchymal stem cells (MSCs) and other mesenchymal progenitors in skeletal regeneration, encompassing bone, cartilage and whole joint regeneration. The expansion reflects developments in the field to include data on the use of MSCs in drug development, growth factors, scaffolds and biomechanical manipulations for skeletal trauma and diseases, including osteoporosis and arthritis. Written for an audience of clinicians and young researchers who are exposed to MSCs in their work, this work summarizes recent findings pertaining to the definition and characterization of MSCs in skeletal tissues and discusses the mechanisms of their actions in regeneration of bone in vivo. The authors describe recent findings pertaining to the efficacy of MSC therapies in animal models and in human clinical trials and bring together literature showing that the ways MSCs are extracted, expanded and implanted can considerably affect bone formation outcomes. Finally, it presents the latest knowledge on the nature of native MSCs in skeletal tissues, which provide a platform for novel in situ tissue regeneration approaches for systemic bone disease such as osteoporosis. Focuses specifically on the use of stem cells in skeletal tissue generation for a broad audience of stem cell, cancer, and bone biologists, orthopedists, oncologists, and regenerative medicine specialists Provides a short historical 'detour' and foundational information on founding concepts, discoveries and personalities in MSC research Assists a new generation of scientists and clinicians in digesting the multitude of journal articles on the topic by providing easily-absorbed and condensed foundational context

Stem Cells

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Publisher : Cambridge University Press
ISBN 13 : 1108663176
Total Pages : 149 pages
Book Rating : 4.1/5 (86 download)

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Book Synopsis Stem Cells by : Melinda Bonnie Fagan

Download or read book Stem Cells written by Melinda Bonnie Fagan and published by Cambridge University Press. This book was released on 2021-05-27 with total page 149 pages. Available in PDF, EPUB and Kindle. Book excerpt: What is a stem cell? The answer is seemingly obvious: a cell that is also a stem, or point of origin, for something else. Upon closer examination, however, this combination of ideas leads directly to fundamental questions about biological development. A cell is a basic category of living thing; a fundamental 'unit of life.' A stem is a site of growth; an active source that supports or gives rise to something else. Both concepts are deeply rooted in biological thought, with rich and complex histories. The idea of a stem cell unites them, but the union is neither simple nor straightforward. This book traces the origins of the stem cell concept, its use in stem cell research today, and implications of the idea for stem cell experiments, their concrete results, and hoped-for clinical advances.

Principles of Regenerative Medicine

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Publisher : Academic Press
ISBN 13 : 9780123814234
Total Pages : 1202 pages
Book Rating : 4.8/5 (142 download)

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Book Synopsis Principles of Regenerative Medicine by : Anthony Atala

Download or read book Principles of Regenerative Medicine written by Anthony Atala and published by Academic Press. This book was released on 2010-12-16 with total page 1202 pages. Available in PDF, EPUB and Kindle. Book excerpt: Virtually any disease that results from malfunctioning, damaged, or failing tissues may be potentially cured through regenerative medicine therapies, by either regenerating the damaged tissues in vivo, or by growing the tissues and organs in vitro and implanting them into the patient. Principles of Regenerative Medicine discusses the latest advances in technology and medicine for replacing tissues and organs damaged by disease and of developing therapies for previously untreatable conditions, such as diabetes, heart disease, liver disease, and renal failure. Key for all researchers and instituions in Stem Cell Biology, Bioengineering, and Developmental Biology The first of its kind to offer an advanced understanding of the latest technologies in regenerative medicine New discoveries from leading researchers on restoration of diseased tissues and organs

Update on Mesenchymal and Induced Pluripotent Stem Cells

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Author :
Publisher :
ISBN 13 : 9781789238082
Total Pages : pages
Book Rating : 4.2/5 (38 download)

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Book Synopsis Update on Mesenchymal and Induced Pluripotent Stem Cells by : Khalid Ahmed Al-Anazi

Download or read book Update on Mesenchymal and Induced Pluripotent Stem Cells written by Khalid Ahmed Al-Anazi and published by . This book was released on 2020 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Human Mesenchymal Stem Cells

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Publisher : Nova Science Publishers
ISBN 13 : 9781536192247
Total Pages : 134 pages
Book Rating : 4.1/5 (922 download)

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Book Synopsis Human Mesenchymal Stem Cells by : Mitchell Khan

Download or read book Human Mesenchymal Stem Cells written by Mitchell Khan and published by Nova Science Publishers. This book was released on 2021 with total page 134 pages. Available in PDF, EPUB and Kindle. Book excerpt: "In Chapter 1, the COVID-19 pandemic and the damage mechanisms on the cellular level which can be ameliorated with the cellular therapies is thoroughly evaluated. Previous and ongoing stem cell clinical trial data from diseases with similar symptoms is gathered. All this accumulated data and current clinical trial results indicate that the cellular therapies could be the most effective treatment option for COVID-19 patients to ameliorate the damaged tissues and save lives. In Chapter 2, the authors examine activated mesenchymal stem cells for stroke repair. Stem Cell treatment has shown recovery in animal models of stroke, indicating an improved regenerative and repair potential. Though stem cells are still being used in clinical trials, there is no evidence that they enhance recovery in ischemic stroke patients. Nevertheless, the multipotent mesenchymal stem has widely been explored for stroke recovery. An'Activated MSC' as a therapeutic alternative to tackling ischemic stroke is proposed, thereby the activation of MSCs by cytokines, growth factors, hypoxia, pharmacological drugs, etc., could be a novel approach to improving stroke patients' responses to receiving MSCs. In Chapter 3, the potential benefits of in vitro culture of therapeutic stem cells in the presence of HB along with the ketogenic diet, whereby higher physiological concentrations of ketone bodies can be achieved in vivo, as an adjuvant to stem cell transplantation is assessed"--