Differentiation And Regulation Of Bone Marrow Mesenchymal Stromal Cells

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 Stromal Cell (MSC) biology has been studied for more than 4 decades and the cells have been investigated for potential clinical applications for more than 15 years. Progress has become exponential over the past decade due mainly to the broad therapeutic potential of these cells. However, MSC studies have also been subject to controversy and increasing scrutiny as new mechanisms of action are reported and ever-expanding therapeutic applications pursued. In this book, leading authorities from all over the world, who are actively involved in this field, provide state-of-the-art knowledge of the basic biology, translational requirements and latest clinical experience with MSCs. This cutting edge book is the ideal resource for scientists and clinicians interested in pursuing an important and rapidly developing field of research that will eventually help patients and address urgent unmet medical needs. Features include: Coverage of the biology of MSCs, latest understanding of mechanisms of action, and role in tissue homeostasis and regeneration Identifying the potential of MSCs in proceeding from bench to bedside from regulatory , GMP production, ethical and safety aspects Critical analysis of clinical studies and the potential of MSCs to treat a wide variety of human diseases and tissues.

This is the first experimental protocol book that covers the differentiation of bone marrow-derived stem cells (BMSCs) into specific cell types, targeted at the undergraduate and graduate student level. The 19 chapters deal with the differentiation methods using small molecules, cytokines and polymeric scaffolds. BMSCs are pluripotential in that they not only act as myelo-regenerative and supportive cells, but can also differentiate into almost any kind of cells in our body. In addition, when implanted in vivo, they could help repair multiple tissues such as blood vessels, heart, liver and so on. For the differentiation of BMSCs, many methods have been introduced to adjust their microenvironment (chemical and physical cues), including chemical induction methods using large or small molecules and pellet culture; mechanical stimulation induction methods using cyclic mechano-transduction or ultrasonication; cytokine-released method using scaffolds; and so on.

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

Stromal cells are connective tissue cells of any organ, and they support the function of the parenchymal cells of that particular organ. Stromal/stromal stem cells are fundamentally a heterogeneous population of cells with contradictory differentiation potential depending upon their environmental niche. Stromal cell biology is not only intriguing, but equally stromal cell ontogeny in vivo remains challenging. In recent years there has been substantial advances in our understanding of stromal cell biology, especially stromal cell isolation, characterization, differentiation, and interactions in physiological (epithelial-stromal interactions) as well as pathophysiological (stromal-cancer interactions) contexts. In addition, stromal cells are also utilized more and more as a therapeutic tool not only in the field of gene therapy but also in the translational field of tissue engineering and regenerative medicine. Therefore, the goal of this book is to consolidate the recent advances in the area of stromal/stromal stem cell biology covering a broad range of interrelated topics in a timely fashion and to disseminate that knowledge in a lucid way to a greater scientific audience. This book will prove highly useful for students, researchers, and clinicians in stem cell biology, developmental biology, cancer biology, pathology, oncology, as well as tissue engineering and regenerative medicine. This quick reference will benefit anyone desiring a thorough overview of stromal cell structure, function, and its therapeutic implications.

The Biology and Therapeutic Application of Mesenchymal Cells comprehensively describes the cellular and molecular biology of mesenchymal stem cells and mesenchymal stromal cells, describing their therapeutic potential in a wide variety of preclinical models of human diseases and their mechanism of action in these preclinical models. Chapters also discuss the current status of the use of mesenchymal stem and stromal cells in clinical trials in a wide range of human diseases and disorders, for many of which there are limited, or no other, therapeutic avenues. Provides coverage on both the biology of mesenchymal stem cells and stromal cells, and their therapeutic applications Describes the therapeutic potential of mesenchymal stem and stromal cells in a wide variety of preclinical models of human diseases and their mechanism of action in these preclinical models Discusses the current status of mesenchymal stem and stromal cells in clinical trials in a wide range of human diseases and disorders, for many of which there are limited, or no other, therapeutic avenues Written and edited by leaders in the field The Biology and Therapeutic Application of Mesenchymal Cells is an invaluable resource for those studying stem cells, cell biology, genetics, gene or cell therapy, or regenerative medicine.