Stem Cell Transplantation – Biology, Processes, Therapy

Anthony D. Ho received his training in internal medicine and hematology-oncology at the University of Heidelberg from 1974 to 1982. He was appointed "Full professor" at the University of Ottawa, Canada, from 1990 to 1992 and at the University of California, San Diego (USCD), from 1992 to 1998. In April 1998 he accepted the present position as Chair of the Department of Medicine V in Heidelberg. His focus of research has been the behavior and biology of marrow-derived stem cells and their applications in clinical transplantation. He is a member of the National Ethics Commission for Stem Cell Research of Robert-Koch-Institute, Berlin. He received the title of Honorary Professor of the Tongji Medical University in Wuhan, China, in October 2003. Ronald Hoffman received his postgraduate training at McGill University in Montreal, Quebec and Stanford University in Palo Alto, California. From 1997 to 1982 he was on the faculty of Yale University School of Medicine. After two years in the industry as vice president of research at Systemix, Inc., he returned to academia to work in his current position as director of the University of Illinois Cancer Center. Dr. Hoffman has published over 240 scientific papers and is the chief editor of one of the most popular books in hematology - Hematology: Basic Principles and Practice. Dr. Hoffman has recently been elected to the prestigious office of President of the American Society of Hematology (ASH). Esmail D. Zanjani obtained his Ph.D. degree from New York University. He is currently Professor of Medicine and Senior Research Career Scientist at University of Nevada School of Medicine in Reno where his research focus is on stem-cell techniques that use sheep to produce humanized organs. Dr. Zanjani has been president of the International Society for Experimental Hematology and currently acts as Editor-in-Chief of the journal Experimental Hematology. He has more than 240 papers to his name and wrote three book chapters.

Preface.List of Contributors.Part I Stem Cell Biology.1 Clinical Potentials of Stem Cells: Hype or Hope? (Anthony D. Ho and Wolfgang Wagner).1.1 Introduction.1.2 What are Stem Cells?1.3 Stem Cells and Regeneration.1.4 Adult and Embryonic Stem Cells.1.5 In the Beginning was the Hematopoietic Stem Cell.1.6 Trans-Differentiation of ASCs.1.7 The Plasticity of ASCs: All Hype and no Hope?1.8 The Battle of Two Cultures: ESCs versus ASCs.1.9 The Challenges for Stem Cell Technology.1.10 Regulation of Self-Renewal versus Differentiation, Asymmetric Divisions.1.11 Genotype and Expression Profiles of Primitive HSCs.1.12 Maintaining Stemness: Interactions between HSCs and the Cellular Microenvironment.1.13 Mesenchymal Stem Cells.1.14 Preliminary Clinical Studies.1.15 Concluding Remarks and Future Perspectives.2 Alteration of Hematopoietic Stem Cell Fates by Chromatin-Modifying Agents (Nadim Mahmud, Mohammed Milhem, Hiroto Araki, and Ronald Hoffman).2.1 Introduction.2.2 Cytotoxicity/Antitumor Activity versus Hypomethylating Effects of 5-Azacytidine and its Analogues.2.3 Treating HSC with 5azaD/TSA can Alter their Fate.2.4 Are the Effects of 5azaD/TSA Due to Cytotoxicity?2.5 Treating HSC with Valproic Acid.2.6 Ex-vivo Expansion of HSC Using Chromatin-Modifying Agents.2.7 Reactivation of Gene Expression by Treating Cells with Chromatin-Modifying Agents.2.8 Alteration of Nonhematopoietic Fate by Chromatin-Modifying Agents.2.9 Safety/Toxicity of Treating Cells with Chromatin-Modifying Agents.2.10 Conclusion.3 Increasing Impact of Micro RNAs in Stem Cell Biology and Medicine (Peter Wernet).3.1 Introduction.3.2 Biogenesis of miRNAs.3.3 Action Modes of miRNAs.3.4 Potential Function Modes of miRNAs.3.5 Conclusions.Part II Standardization and Quality Assurance of Stem Cell Preparations.4 Novel Strategies for the Mobilization of Hematopoietic Stem Cells (Stefan Fruehauf, Timon Seeger, and Julian Topaly).4.1 Physiology of Blood Stem Cell Mobilization.4.2 Innovative Agents for PBPC Mobilization.5 Pluripotent Stem Cells from Umbilical Cord Blood (Gesine Kogler and Peter Wernet).5.1 Biological Advantages of Cord Blood as a Stem Cell Resource.5.2 The Generation and Expansion of Pluripotent Cells (USSC) from Cord Blood.5.3 Other Multipotent Nonhematopoietic Stem Cells: Mesenchymal Cells in CB and CB Tissue.5.4 Conclusion: Future Efforts Towards the Regenerative Capacity of CB Nonhematopoietic Cells.6 Good Manufacturing Practices: Clinical-Scale Production of Mesenchymal Stem Cells (Luc Sensebe, Philippe Bourin, and Luc Douay).6.1 Introduction.6.2 Prerequisites for the Clinical-Scale Production of MSCs.6.3 Clinical-Scale Production: the French Experience.6.4 QA and QC.6.5 Future Prospects.7 The Clonal Activity of Marked Hematopoietic Stem Cells (Jingqiong Hu, Manfred Schmidt, Annette Deichmann, Hanno Glimm, and Christof von Kalle).7.1 Introduction.7.2 Characterization of In-vivo Clonal Activity of HSCs by Genetic Marking.7.3 Retroviral Integration Site Analysis.7.4 Clonality Analysis in Animal Model and Human Gene Therapy Trials.7.5 Interaction of Retroviral Integration Site and Transgene Expression with Clonal Activity of the Respective HSC.7.6 Clinical Interventions Affect the Clonal Activity of Marked HSCs.7.7 Perspectives.Part III On the Threshold to Clinical Applications.8 ALarge Animal Non-Injury Model for Study of Human Stem Cell Plasticity (Graca Almeida-Porada, Christopher D. Porada, and Esmail D. Zanjani).8.1 Introduction.8.2 The Uniqueness of the Fetal Sheep Model.8.3 Differentiative Potential of Human Cells in the Fetal Sheep Model.9 Developmental Potential of Somatic Stem Cells Following Injection into Murine Blastocysts (Michael Durr, Friedrich Harder, and Albrecht M. Muller).9.1 Introduction.9.2 Neurosphere Cells Generate Erythroid-Like Cells Following Injection into Early Embryos.9.3 Hematopoietic Chimerism by Human Cord Blood-Derived HSCs.9.4 Injection of Leukemic Cells into Blastocysts.9.5 Discussion.10 Testing the Limits: The Potential of MAPC in Animal Models (Felipe Prosper and Catherine M. Verfaillie).10.1 Introduction.10.2 Characterization of MAPCs.10.3 In-Vitro Differentiation Potential of MAPCs.10.4 In-Vivo Differentiation Potential of MAPCs.10.5 Mechanisms Underlying the Phenomenon of MAPCs.10.6 Conclusion.11 Mesenchymal Stem Cells as Vehicles for Genetic Targeting of Tumors (Frank Marini, Brett Hall, Jennifer Dembinski, Matus Studeny, A. Kate Sasser, and Michael Andreeff).11.1 Introduction.11.2 The Tumor Stroma and its Components.11.3 The Role of Tumor-Stroma Interactions in Tumor Progression.11.4 The Similarity of MSC Tumor Tropism to Wound Healing.11.5 The Rationale for using MSCs as Cellular Delivery Vehicles.11.6 The Challenges in Developing MSC-Based Delivery Strategies.11.7 Conclusions.Part IV Clinical Trials.12 Endothelial Progenitor Cells for Cardiac Regeneration (Ulrich Fischer-Rasokat and Stefanie Dimmeler).12.1 Characterization of Endothelial Progenitor Cells.12.2 Functions of EPCs to Improve Cardiac Function.12.3 Mechanisms of Homing.12.4 Results from Clinical Studies.613 Stem Cells and Bypass Grafting for Myocardial and Vascular Regeneration (Christof Stamm, Dirk Strunk, and Gustav Steinhoff).13.1 Introduction.13.2 Coronary Artery Disease.13.3 Indications for CABG Surgery.13.4 The Rationale for Cell Therapy in CABG Patients.13.5 The Role of Bone Marrow Cells.13.6 Combination of (Stem) Cell Treatment with CABG Surgery.13.7 Outlook.14 Adoptive Immunotherapy: Guidelines and Clinical Practice (Hans-Jochem Kolb, Christoph Schmid, Iris Bigalke, Raymund Buhmann, Belinda Simoes, Ting Yang, Johanna Tischer, Michael Stanglmaier, Horst Lindhofer, Christine Falk, and Georg Ledderose).14.1 Introduction.14.2 Animal Experiments.14.3 The First Clinical Results in CML.14.4 The EBMT Study.14.5 The Graft-versus-Leukemia Effect.14.6 Cytokines.14.7 Bispecific Antibodies.14.8 NK and NK-T Cells and HLA-Haploidentical Transplantation.14.9 Outlook of Adoptive Immunotherapy in Chimerism.15 Immune Escape and Suppression by Human Mesenchymal Stem Cells (Katarina Le Blanc and Olle Ringden).15.1 Introduction.15.2 MSCs Escape the Immune System.15.3 Immunosuppression by MSCs.15.4 MSC in the Clinic.16 Stem Cell Transplantation: The Basis for Successful Cellular Immunotherapy (Peter Dreger, Matthias Ritgen, and Anthony D. Ho).16.1 Introduction.16.2 Allogeneic Stem Cell Transplantation in CLL.16.3 Graft-versus-Leukemia Effect in CLL.16.4 Allo-SCT with Reduced-Intensity Conditioning in CLL.16.5 RICT from Unrelated Donors.16.6 T-Cell Depletion.16.7 Allo-SCT in Follicular Lymphoma.16.8 Allo-SCT in Waldenstrom's Disease.16.9 Conclusions and Perspectives.Index.