Stem cell transplantation : biology, processing, and therapy /

Table Of Contents:
Preface xiii

List of Contributors xv

Part I Stem Cell Biology

Clinical Potentials of Stem Cells: Hype or Hope? 3(24)

Anthony D. Ho

Wolfgang Wagner

Introduction 3(1)

What are Stem Cells? 3(1)

Stem Cells and Regeneration 4(2)

Adult and Embryonic Stem Cells 6(1)

In the Beginning was the Hematopoietic Stem Cell 7(1)

Trans-Differentiation of ASCs 8(1)

The Plasticity of ASCs: All Hype and no Hope? 9(1)

The Battle of Two Cultures: ESCs versus ASCs 10(1)

The Challenges for Stem Cell Technology 11(1)

Regulation of Self-Renewal versus Differentiation, Asymmetric Divisions 12(2)

Genotype and Expression Profiles of Primitive HSCs 14(1)

Maintaining Stemness: Interactions between HSCs and the Cellular Microenvironment 15(1)

Mesenchymal Stem Cells 16(2)

Preliminary Clinical Studies 18(1)

Concluding Remarks and Future Perspectives 19(8)

Alteration of Hematopoietic Stem Cell Fates by Chromatin-Modifying Agents 27(16)

Nadim Mahmud

Mohammed Milhem

Hiroto Araki

Ronald Hoffman

Introduction 27(2)

Cytotoxicity/Antitumor Activity versus Hypomethylating Effects of 5-Azacytidine and its Analogues 29(1)

Treating HSC with 5azaD/TSA can Alter their Fate 30(2)

Are the Effects of 5azaD/TSA Due to Cytotoxicity? 32(1)

Treating HSC with Valproic Acid 33(1)

Ex-vivo Expansion of HSC Using Chromatin-Modifying Agents 33(1)

Reactivation of Gene Expression by Treating Cells with Chromatin-Modifying Agents 34(1)

Alteration of Nonhematopoietic Fate by Chromatin-Modifying Agents 35(1)

Safety/Toxicity of Treating Cells with Chromatin-Modifying Agents 36(1)

Conclusion 37(6)

Increasing Impact of Micro RNAs in Stem Cell Biology and Medicine 43(14)

Peter Wernet

Introduction 43(1)

Biogenesis of miRNAs 44(2)

Action Modes of miRNAs 46(2)

Potential Function Modes of miRNAs 48(2)

Conclusions 50(7)

Part II Standardization and Quality Assurance of Stem Cell Preparations

Novel Strategies for the Mobilization of Hematopoietic Stem Cells 57(16)

Stefan Fruehauf

Timon Seeger

Julian Topaly

Physiology of Blood Stem Cell Mobilization 57(6)

Stromal-Derived Factor-1 Alpha (SDF-1α)/CXCR4 Pathway 58(5)

Innovative Agents for PBPC Mobilization 63(10)

AMD-3100 63(2)

CTCE0021 and CTCE0214 65(1)

C3aR Antagonist SB 290157 66(1)

GROβT (CXCL2Δ4) 66(7)

Pluripotent Stem Cells from Umbilical Cord Blood 73(18)

Gesine Kogler

Peter Wernet

Biological Advantages of Cord Blood as a Stem Cell Resource 73(1)

The Generation and Expansion of Pluripotent Cells (USSC) from Cord Blood 74(11)

Generation and Expansion of USSC from Fresh CB 74(2)

Generation and Expansion of USSC from Cryoconserved CB 76(1)

Immunophenotype of USSC Obtained from Fresh and Cryopreserved CB Specimens 77(1)

Expansion of USSC 77(1)

The Differentiation Potential of USSC 77(1)

In-vitro and In-vivo Differentiation of USSC into Mesenchymal Cell Lineages 77(3)

Differentiation of USSC into Neural Cells In Vitro and In Vivo 80(1)

Application of USSC to the Fetal Sheep Xenograft Model to Study In-vivo Hematopoiesis 80(1)

In-vivo Differentiation of USSC into Myocardial Cells and Purkinje Fibers in the Preimmune Fetal Sheep 81(1)

In-vivo Differentiation of USSC into Hepatic Cells in the Preimmune Fetal Sheep 81(1)

Cytokine Production and Hematopoiesis Supporting Activity of CB-Derived Unrestricted Somatic Stem Cells 82(1)

Rationale for Application of USSC to Support Hematopoiesis 82(1)

Qualitative and Quantitative Assessment of Cytokines Produced by USSC or Bone Marrow MSC 83(1)

Hematopoiesis Supporting Stromal Activity of USSC in Comparison to BM MSC 84(1)

Other Multipotent Nonhematopoietic Stem Cells: Mesenchymal Cells in CB and CB Tissue 85(1)

Conclusion: Future Efforts Towards the Regenerative Capacity of CB Nonhematopoietic Cells 85(6)

Good Manufacturing Practices: Clinical-Scale Production of Mesenchymal Stem Cells 91(16)

Luc Sensebe

Philippe Bourin

Luc Douay

Introduction 91(1)

Prerequisites for the Clinical-Scale Production of MSCs 92(5)

Starting Material 92(1)

Are there Alternative Sources of MSCs? 93(1)

Cell Plating Density 94(1)

Number of Passages 95(1)

Medium 95(1)

Culture with Biomaterials 96(1)

Clinical-Scale Production: the French Experience 97(2)

Culture Conditions 97(1)

Devices for MSC Culture 98(1)

QA and QC 99(3)

French Experimental System GESAQ 99(1)

Quality Controls 100(1)

Control of the Harvested Graft 100(2)

Controls During Culture 102(1)

Controls During Release of the Graft 102(1)

Future Prospects 102(5)

The Clonal Activity of Marked Hematopoietic Stem Cells 107(14)

Jingqiong Hu

Manfred Schmidt

Annette Deichmann

Hanno Glimm

Christof von Kalle

Introduction 107(1)

Characterization of In-vivo Clonal Activity of HSCs by Genetic Marking 107(1)

Retroviral Integration Site Analysis 108(1)

Clonality Analysis in Animal Model and Human Gene Therapy Trials 109(4)

Clonal Activity of Marked HSCs in Mouse Models 109(1)

Clonal Activity of Marked HSCs in Non-Human Primate Models 110(1)

Clonal Activity of Marked HSCs in Human Gene Therapy Clinical Trials 110(1)

Clonality Analysis in ADA-SCID Gene Therapy Clinical Trial 110(1)

Clonality Analysis in SCID-X1 Gene Therapy Clinical Trial 111(1)

LMO2 Insertion Leads to Malignant Expansion of Marked HSCs 112(1)

Interaction of Retroviral Integration Site and Transgene Expression with Clonal Activity of the Respective HSC 113(1)

Impact of Transgene Expression on Clonal Activity of Marked HSCs 114(1)

Clinical Interventions Affect the Clonal Activity of Marked HSCs 114(1)

Perspectives 115(6)

Part III On the Threshold to Clinical Applications

A Large Animal Non-Injury Model for Study of Human Stem Cell Plasticity 121(12)

Graca Almeida-Porada

Christopher D. Porada

Esmail D. Zanjani

Introduction 121(2)

The Uniqueness of the Fetal Sheep Model 123(3)

Differentiative Potential of Human Cells in the Fetal Sheep Model 126(7)

Developmental Potential of Somatic Stem Cells Following Injection into Murine Blastocysts 133(14)

Michael Durr

Friedrich Harder

Albrecht M. Muller

Introduction 133(1)

Neurosphere Cells Generate Erythroid-Like Cells Following Injection into Early Embryos 134(4)

Hematopoietic Chimerism by Human Cord Blood-Derived HSCs 138(1)

Injection of Leukemic Cells into Blastocysts 138(2)

Discussion 140(7)

Testing the Limits: The Potential of MAPC in Animal Models 147(10)

Felipe Prosper

Catherine M. Verfaillie

Introduction 147(1)

Characterization of MAPCs 148(2)

Phenotype of MAPCs 148(1)

Proliferative Capacity of MAPCs and Culture Conditions 148(2)

In-Vitro Differentiation Potential of MAPCs 150(1)

In-Vivo Differentiation Potential of MAPCs 150(2)

Mechanisms Underlying the Phenomenon of MAPCs 152(2)

Conclusion 154(3)

Mesenchymal Stem Cells as Vehicles for Genetic Targeting of Tumors 157(22)

Frank Marini

Brett Hall

Jennifer Dembinski

Matus Studeny

A. Kate Sasser

Michael Andreeff

Introduction 157(1)

The Tumor Stroma and its Components 158(3)

The Role of Tumor-Stroma Interactions in Tumor Progression 161(1)

The Similarity of MSC Tumor Tropism to Wound Healing 162(1)

The Rationale for using MSCs as Cellular Delivery Vehicles 162(5)

Recent Studies of MSC as Cellular Vehicles 164(3)

The Challenges in Developing MSC-Based Delivery Strategies 167(1)

Conclusions 167(12)

Part IV Clinical Trials

Endothelial Progenitor Cells for Cardiac Regeneration 179(18)

Ulrich Fischer-Rasokat

Stefanie Dimmeler

Characterization of Endothelial Progenitor Cells 179(2)

Functions of EPCs to Improve Cardiac Function 181(3)

Improvement of Neovascularization 182(1)

Paracrine Effects 183(1)

Differentiation and/or Fusion 183(1)

Mechanisms of Homing 184(2)

Adhesion 184(2)

Chemotaxis, Migration, and Invasion 186(1)

Results from Clinical Studies 186(11)

Stem/Progenitor Cell Therapy in Patients after Acute Myocardial Infarction 189(1)

Stem/Progenitor Cell Therapy in Patients with Chronic Ischemic Heart Failure 190(7)

Stem Cells and Bypass Grafting for Myocardial and Vascular Regeneration 197(24)

Christof Stamm

Dirk Strunk

Gustav Steinhoff

Introduction 197(1)

Coronary Artery Disease 198(1)

Myocardial Ischemia 198(1)

Indications for CABG Surgery 199(3)

Outcome of CABG Surgery 200(1)

Technique of CABG Surgery 201(1)

The Rationale for Cell Therapy in CABG Patients 202(1)

The Role of Bone Marrow Cells 202(5)

Bone Marrow Cells and Angiogenesis 202(3)

Bone Marrow Cells and Myogenesis 205(2)

Combination of (Stem) Cell Treatment with CABG Surgery 207(9)

Skeletal Myoblasts 207(2)

Bone Marrow Mononuclear Cells 209(1)

Bone Marrow Stem Cells 210(2)

Cell Preparation 212(2)

Surgery 214(1)

Preliminary Results 214(2)

Outlook 216(5)

Adoptive Immunotherapy: Guidelines and Clinical Practice 221(12)

Hans-Jochem Kolb

Christoph Schmid

Iris Bigalke

Raymund Buhmann

Belinda Simoes

Ting Yang

Johanna Tischer

Michael Stanglmaier

Horst Lindhofer

Christine Falk

Georg Ledderose

Introduction 221(1)

Animal Experiments 222(1)

The First Clinical Results in CML 222(1)

The EBMT Study 222(2)

The Graft-versus-Leukemia Effect 224(1)

Cytokines 225(2)

Bispecific Antibodies 227(1)

NK and NK-T Cells and HLA-Haploidentical Transplantation 228(1)

Outlook of Adoptive Immunotherapy in Chimerism 229(4)

Immune Escape and Suppression by Human Mesenchymal Stem Cells 233(14)

Katarina Le Blanc

Olle Ringden

Introduction 233(1)

MSCs Escape the Immune System 234(1)

Immunosuppression by MSCs 235(4)

MSC in the Clinic 239(8)

Stem Cell Transplantation: The Basis for Successful Cellular Immunotherapy 247(14)

Peter Dreger

Matthias Ritgen

Anthony D. Ho

Introduction 247(1)

Allogeneic Stem Cell Transplantation in CLL 247(2)

Graft-versus-Leukemia Effect in CLL 249(1)

Allo-SCT with Reduced-Intensity Conditioning in CLL 249(2)

RICT from Unrelated Donors 251(1)

T-Cell Depletion 252(1)

Allo-SCT in Follicular Lymphoma 253(2)

Allo-SCT in Waldenstrom's Disease 255(2)

Conclusions and Perspectives 257(4)
Index 261