In Vitro Study of Bone Marrow Derived Progenitor Cells in Liver-like Microenvironments


Book Description

Published observations of the 'in vivo' differentiation of bone marrow (BM) derived cells into hepatocytes led us to study the mechanisms that regulate this differentiation 'in vitro'. Phenotypically defined (Lin-) BM populations were cultured in microenvironments that mimic parenchymal and nonparenchymal liver components. A significant difference in the spectrum of cells generated from BM under various conditions was observed. Specifically, enriched BM cells gave rise to endoderm-like cells in co-culture with fibroblasts. Lin- cells were shown to generate liver-like cells that expressed CK8 and albumin upon exposure to high HGF-concentrations. Also, individual hematopoietic stem cells (HSC - c-kit+ Lin - Sca-1+) were shown to give rise to albumin-secreting cells, in presence of HGF while the addition of hematopoietic cytokines decreased the frequency of hepatic progeny. These results suggest that HGF is an important regulator of HSC, which may act in inducing HSC to give rise to hematopoietic or hepatic progeny.




Bone Marrow-Derived Progenitors


Book Description

The ambitious goal of this volume is to provide – in chapters written by accomplished scientists and experts in their field – a comprehensive overview of the currently available information related to the therapeutic utility of adult bone marrow-derived cells. With excitement generated almost daily about the possible uses of stem cells to treat human disease, but the controversy surrounding their use still raging, adult bone-marrow derived cells are more readily available, and have a staggering range of uses.




In Vitro Processing of Human Bone Marrow Derived Mesenchymal Stem Cells to Enhance Delivery in Liver Disease


Book Description

Currently the only effective treatment for end stage liver disease is transplantation together with immune-modulating drugs. Human bone marrow derived mesenchymal stem cells (MSC) have been shown to suppress inflammation, potentiate regeneration and act as vectors for gene therapy. Thus, MSC infusions offer an attractive potential therapy for treating liver disease. However a number of obstacles exist in MSC delivery before they can be used therapeutically. Although MSC can migrate to sites of injury after in vivo administration, their engraftment within the liver is often poor, potentially limiting their therapeutic action. I have shown that detaching MSC from culture using non-enzymatic methods is superior in retaining surface chemokine receptor expression. Furthermore, I have shown that these receptors are functional in migration and attachment assays both in vitro and in vivo in carbon-tetrachloride induced liver injury. TGF[beta]1 stimulated MSC were able to further enhance engraftment via up-regulation of surface CXCR3. Additionally the potent immunosuppressive properties of MSC, mediated via Prostaglandin E2, were enhanced after TGF[beta]1 stimulation. Thus my studies demonstrate that manipulation of MSC through careful choice of detachment methods and exogenous cytokine stimulation can improve their engraftment in injured liver and their immunosuppressive properties with implications for improving the efficacy of MSC therapy.




Hematopoietic Stem Cell Development


Book Description

This book collects articles on the biology of hematopoietic stem cells during embryonic development, reporting on fly, fish, avian and mammalian models. The text invites a comparative overview of hematopoietic stem cell generation in the different classes, emphasizing conserved trends in development. The book reviews current knowledge on human hematopoietic development and discusses recent breakthroughs of relevance to both researchers and clinicians.




Fibrosis Research


Book Description

Leading investigators review the highlights of current fibrosis research and the experimental methodologies used uncover the mechanisms that drive it. In their discussion of research methodologies utilizing cultured cells to model various aspects of the fibrotic response in vitro, the authors describe the isolation, characterization, and propagation of mesenchymal cells, and highlight the similarities and differences between methods that are appropriate for different types of fibroblasts. Approaches for studying collagen gene regulation and TGF-b production are also discussed, along with experimental methodologies utilizing animal models to study the pathogenesis of fibrosis. The protocols follow the successful Methods in Molecular MedicineTM series format, each offering step-by-step laboratory instructions, an introduction outlining the principles behind the technique, lists of the necessary equipment and reagents, and tips on troubleshooting and avoiding known pitfalls.




Mesenchymal Stem Cell Therapy


Book Description

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.




Muse Cells


Book Description

This book provides the first comprehensive account of multilineage-differentiating stress-enduring (Muse) cells, a pluripotent and non-tumorigenic subpopulation of mesenchymal stem cells (MSCs) that have the ability to detect damage signals, migrate to damaged sites, and spontaneously differentiate into cells compatible with the affected tissue, thereby enabling repair of all tissue types. The coverage encompasses everything from the basic properties of Muse cells to their tissue repair effects and potential clinical applications—for example, in acute myocardial infarction, stroke, skin injuries and ulcers, renal failure, and liver disease. An important technical chapter provides a practical and precise protocol for the isolation of Muse cells, which will enable readers to use Muse cells in their own research. In offering fascinating insights into the strategic organization of the body’s reparative function and explaining how full utilization of Muse cells may significantly enhance the effectiveness of MSC treatment, the book will be of high value for Ph.D. students, postdocs, basic researchers, clinical doctors, and industrial developers.




Handbook of Pediatric Transfusion Medicine


Book Description

Structured to be a companion to the recently published Handbook of Transfusion Medicine, the Handbook of Pediatric Transfusion Medicine is dedicated to pediatric hematology-oncology and transfusion medicine, a field which remains ambiguous and which has generated few comprehensive texts. This book stands alone as one of the few texts that addresses transfusion issues specific to pediatric medicine. Written in an eminently readable style, this authoritative handbook is a requirement for any pediatric physician or caregiver. Neonatal and fetal immune response and in utero development issues Blood compatability and pre-transfusion testing issues specific to pediatric and neonatal transfusion Therapeutic apheresis including red blood cell exchange and prophylactic chronic erythrocytapheresis for sickle cell patients Also includes a section that concentrates on the consent, quality and legal issues of blood transfusion and donation




Geriatric Oncology


Book Description

This book is intended as a comprehensive resource for clinicians and researchers seeking in-depth information on geriatric oncology. The coverage encompasses epidemiology, the biology and (patho)physiology of aging and cancer, geriatric assessment and management, hematologic malignancies, solid tumors, issues in patient care, and research methods. Since cancer is a disease of aging and people are living longer, most cancer patients are now aged 70 and older. Yet the more we age, the more diverse we become in terms of our health, biologic fitness, and cancer behavior. Typically, however, general oncology clinical trials address only a selected healthier and younger population of patients. Geriatric oncology is the area of oncology that addresses these issues but while a wealth of knowledge has been accumulated, information is often difficult to retrieve or insufficiently detailed. The SpringerReference program, in which this book is published, offers an ideal format for overcoming these limitations since it combines thorough coverage with access to living editions constantly updated chapter by chapter via a dynamic peer-review process, ensuring that information remains current and pertinent.