Male Germline Stem Cells: Developmental and Regenerative Potential

Developmental and Regenerative Potential
1. Auflage 2010
ISBN: 978-1-61737-973-4
Verlag: Humana Press
Format: PDF
Kopierschutz: Wasserzeichen (»Systemvoraussetzungen)

E-Book, Englisch, 262 Seiten

Scientists investigating germ cells have, over the past 15 years, originated discoveries and innovations that give us valuable insights into the mechanisms that regulate not just stem cell function, but human development in its widest sense. With contributions from some of the leading researchers in the field, Male Germline Stem Cells: Developmental and Regenerative Potential assesses the implications of these discoveries for understanding the fundamental biology of germline stem cells as well as their potential for human stem cell-based therapies. This monograph covers many of the fundamental issues now being explored by today's generation of stem cell researchers, including the field's potential for regenerative medicine. Ranging from an assessment of the pluripotency of primordial germ cells and their possible applications in treating testicular cancer, to the recovery of once-mordant fertilization-competent sperm, this volume has it all. It is a reference point for any scientist involved in related research as well as being a timely summation of what could prove to be a hugely exciting and very fruitful area of inquiry.

Autoren/Hrsg.

Inhaltsverzeichnis

1;Male Germline Stem Cells:Developmental andRegenerative Potential;3
1.1;Foreword;5
1.2;Contents;9
1.3;Contributors;15
1.4;Part I:Germline Developmental Potential;19
1.4.1;Chapter 1: Pathways to Pluripotency: How Germ Cells Make Stem Cells;20
1.4.1.1;1.1 Introduction;20
1.4.1.2;1.2 Early Germ Cell Development;22
1.4.1.3;1.3 How It All Goes Wrong;24
1.4.1.4;1.4 Probing the Mechanisms of Pluripotency;27
1.4.1.5;1.5 Lessons from Testicular Cancer;32
1.4.1.6;1.6 Parallel Pathways to Pluripotency;37
1.4.1.7;References;38
1.4.2;Chapter 2: Pluripotent Stem Cells from the Postnatal Testis: Unlocking the Potential of Spermatogonial Stem Cells;42
1.4.2.1;2.1 Introduction;42
1.4.2.2;2.2 The Putative Precursors: Spermatogonial Stem Cells (SSCs);43
1.4.2.3;2.3 Molecular Features that Could Predispose SSCs to Pluripotency;44
1.4.2.4;2.4 Epigenetic Factors that Could Predispose to Pluripotency;47
1.4.2.5;2.5 Culture-Induced Pluripotency in Mice;48
1.4.2.6;2.6 Culture-Induced Pluripotency in Humans;53
1.4.2.7;2.7 Potential Applications of Germline-Derived Pluripotent Cells: A Comparison with ES Cells and iPS Cells;55
1.4.2.8;2.8 Conclusions;58
1.4.2.9;2.9 Addendum;59
1.4.2.10;References;59
1.4.3;Chapter 3: Making Germ Cells from Human Embryonic Stem Cells;65
1.4.3.1;3.1 Introduction;66
1.4.3.2;3.2 The Formation and Differentiation of Gametes In Vivo;68
1.4.3.2.1;3.2.1 Germ Plasm Versus Inductive Signaling;68
1.4.3.2.2;3.2.2 The Morphological Features of Gamete Development;69
1.4.3.2.3;3.2.3 The Molecular Requirements of Germ Cell Development;71
1.4.3.3;3.3 The DAZ Gene Family;73
1.4.3.3.1;3.3.1 The Y Chromosome DAZ Genes;73
1.4.3.3.2;3.3.2 DAZ Family Genes Are Evolutionarily Conserved and Function in Gametogenesis;74
1.4.3.4;3.4 The Generation of Germ Cells from ES Cells In Vitro;78
1.4.3.4.1;3.4.1 Similarities Between ES Cells and Germ Cells;79
1.4.3.4.2;3.4.2 Can Human ES Cells Give Rise to Germ Cells?;80
1.4.3.4.3;3.4.3 Generation of Mouse Germ Cells and Gametes In Vitro;82
1.4.3.4.4;3.4.4 Generation and Isolation of Human Germ Cells In Vitro;84
1.4.3.5;3.5 Genetic Requirements of Making Germ Cells;88
1.4.3.5.1;3.5.1 Key Germ Cell Genes;88
1.4.3.5.2;3.5.2 Definitive Proof of Mature Germ Cell Formation;91
1.4.3.6;3.6 The Future: Improved Methods and Clinical Implications;93
1.4.3.6.1;3.6.1 Improving Culture Conditions for Enhanced Gamete Formation;93
1.4.3.6.2;3.6.2 Clinical Implications and Outlook;93
1.4.3.7;References;95
1.5;Part II:Spermatogonial Stem Cells;103
1.5.1;Chapter 4: Morphometric Description of Spermatogonial Stem Cells and Expansion of Their Clonal Derivatives;104
1.5.1.1;4.1 Outline;105
1.5.1.2;4.2 Introduction;105
1.5.1.3;4.3 Scheme of Spermatogonial Multiplication and Stem Cell Renewal;106
1.5.1.4;4.4 Morphological Characteristics of As,.pr,.al Spermatogonia;107
1.5.1.5;4.5 Numbers of As,pr,al Spermatogonia During the Epithelial Cycle;110
1.5.1.6;4.6 Cell Cycle Characteristics of As,pr,al Spermatogonia;111
1.5.1.7;4.7 The Occurrence of “False” Pairs of Spermatogonia;113
1.5.1.8;4.8 Proliferative Activity of As, Apr, and Aal Spermatogonia During the Epithelial Cycle;114
1.5.1.9;4.9 Regulation of the Proliferative Activity of As, Apr, and Aal Spermatogonia at the Cellular Level;115
1.5.1.10;4.10 Regulation of Spermatogonial Numbers;117
1.5.1.11;4.11 Conclusion;118
1.5.1.12;References;118
1.5.2;Chapter 5: Spermatogonial Stem Cell Transplantation and Culture;121
1.5.2.1;5.1 Introduction;122
1.5.2.2;5.2 Spermatogonial Stem Cell Transplantation;122
1.5.2.2.1;5.2.1 History;122
1.5.2.2.2;5.2.2 Implications;122
1.5.2.2.3;5.2.3 Clonality and Quantification;124
1.5.2.2.4;5.2.4 Species Specificity;124
1.5.2.2.4.1;5.2.4.1 Rodent;124
1.5.2.2.4.2;5.2.4.2 Non-rodents;124
1.5.2.2.5;5.2.5 Procedures and Considerations;125
1.5.2.2.5.1;5.2.5.1 Cell Labeling and Enrichment;125
1.5.2.2.5.2;5.2.5.2 Homing Efficiency;126
1.5.2.2.5.3;5.2.5.3 Recipient Preparation and Injection;128
1.5.2.3;5.3 Spermatogonial Stem Cell Culture;129
1.5.2.3.1;5.3.1 History;129
1.5.2.3.2;5.3.2 Implications;130
1.5.2.3.3;5.3.3 Short- Versus Long-Term Culture;130
1.5.2.3.4;5.3.4 Species;133
1.5.2.3.4.1;5.3.4.1 Rodent;133
1.5.2.3.4.2;5.3.4.2 Non-rodent;134
1.5.2.4;5.4 Summary;134
1.5.2.5;References;134
1.5.3;Chapter 6: The Cluster-Forming Activity Assay: A Short-Term In Vitro Method to Analyze the Activity of Mouse Spermatogonial Stem Cells;138
1.5.3.1;6.1 Parallelism Between the Results of In Vitro and In Vivo SSC Assays;139
1.5.3.2;6.2 Advantages of the CFA Assay;141
1.5.3.3;6.3 Cautionary Issues;142
1.5.3.3.1;6.3.1 Does the CFA Assay Assess the Full Range of Stem Cell Characteristics?;142
1.5.3.3.2;6.3.2 Do Clusters Arise Only from SSCs?;142
1.5.3.3.3;6.3.3 Does the Number of Cells Placed in Culture Affect Assay Outcomes?;143
1.5.3.3.4;6.3.4 Can the CFA Assay Distinguish SSC Proliferation and Maintenance?;143
1.5.3.3.5;6.3.5 Is Cluster Number the Only Readout of the CFA Assay?;145
1.5.3.3.6;6.3.6 Other Considerations;145
1.5.3.4;6.4 Future Prospects;146
1.5.3.5;References;146
1.5.4;Chapter 7: Molecular Mechanisms Regulating Spermatogonial Stem Cell Fate Decisions;148
1.5.4.1;7.1 Spermatogenesis and Spermatogonial Stem Cell Biology;149
1.5.4.2;7.2 Extrinsic Growth Factor Regulation of SSC Self-renewal;152
1.5.4.2.1;7.2.1 GDNF;152
1.5.4.2.2;7.2.2 FGF2 and CSF1;154
1.5.4.3;7.3 Internal Molecular Pathways Regulating SSC Self-Renewal;154
1.5.4.3.1;7.3.1 GDNF-Regulated Gene Expression in Mouse SSCs;155
1.5.4.3.2;7.3.2 GDNF-Regulated Transcription Factors;156
1.5.4.3.2.1;7.3.2.1 BCL6B;156
1.5.4.3.2.2;7.3.2.2 ETV5;157
1.5.4.3.2.3;7.3.2.3 LHX1;157
1.5.4.3.2.4;7.3.2.4 OCT6;158
1.5.4.3.3;7.3.3 Non-GDNF Regulated Transcription/Translation Factors;158
1.5.4.3.3.1;7.3.3.1 MILI;158
1.5.4.3.3.2;7.3.3.2 NANOS2;159
1.5.4.3.3.3;7.3.3.3 OCT3/4;160
1.5.4.3.3.4;7.3.3.4 PLZF;160
1.5.4.3.3.5;7.3.3.5 TAF4B;162
1.5.4.3.4;7.3.4 Transcription Factors with Putative Roles in SSC Differentiation;162
1.5.4.3.4.1;7.3.4.1 NGN3;163
1.5.4.3.4.2;7.3.4.2 SOHLH1;163
1.5.4.4;7.4 GDNF-Activated Signaling Pathways in Cultured Mouse SSCs;163
1.5.4.5;7.5 Summary;164
1.5.4.6;References;166
1.5.5;Chapter 8: Stem Cell Niche System in Mouse Spermatogenesis;171
1.5.5.1;8.1 Introduction;171
1.5.5.2;8.2 Drosophila Germline Stem Cell Niche System;172
1.5.5.3;8.3 Architecture of the Mouse Testis;174
1.5.5.4;8.4 Mouse Spermatogenic Stem Cells;176
1.5.5.5;8.5 Niche Microenvironment in the Mouse Testis;178
1.5.5.6;8.6 Molecular Mechanisms That Could Be Involved in the Niche Functions;181
1.5.5.6.1;8.6.1 Soluble Factors;181
1.5.5.6.1.1;8.6.1.1 GDNF (Glial Cell Line-Derived Neurotrophic Factor) Signaling;181
1.5.5.6.1.2;8.6.1.2 CSF1 (Colony Stimulating Factor 1/Macrophage Colony-Stimulating Factor or M-CSF) Signaling;182
1.5.5.6.2;8.6.2 FGF (Fibroblast Growth Factor) and Other Factors;183
1.5.5.7;8.7 Cell–Cell Contact and Basement Membrane Binding;183
1.5.5.8;8.8 Transcriptional Regulator in Somatic Cells;184
1.5.5.8.1;8.8.1 Etv5 (ets Variant Gene 5/ERM or ets-Related Molecule);184
1.5.5.9;8.9 Conclusion;184
1.5.5.10;References;185
1.6;Part III: Translation and Regenerative Potentialof Spermatogonial Stem Cells;188
1.6.1;Chapter 9: Regenerative Potential of Spermatogenesisafter Gonadotoxic Therapies;189
1.6.1.1;9.1 Introduction;189
1.6.1.2;9.2 Immediate and Short-Term Effects of Gonadotoxic Therapies;190
1.6.1.3;9.3 Stem Spermatogonial Survival–Methods;192
1.6.1.4;9.4 Stem Spermatogonial Survival-Results;193
1.6.1.4.1;9.4.1 Counts of Type A Spermatogonia;193
1.6.1.4.2;9.4.2 Assessing Stem Cell Survival by Recovery Potential;194
1.6.1.4.3;9.4.3 Functional Assay of Stem Cells by Transplantation;197
1.6.1.5;9.5 Recovery of Spermatogenesis from Surviving Stem Spermatogonia;197
1.6.1.6;9.6 Modulation of the Regenerative Process;201
1.6.1.7;9.7 Analysis of Interspecies Differences;204
1.6.1.8;9.8 Conclusion;206
1.6.1.9;References;207
1.6.2;Chapter 10: Testicular Xenografting;214
1.6.2.1;10.1 Introduction;215
1.6.2.2;10.2 Testicular Tissue Grafting: A Comparative Overview;216
1.6.2.3;10.3 Testicular Xenografting Using Testicular Cell Suspensions;227
1.6.2.4;10.4 Xenografting of Primate Testicular Tissue: Clinical and Experimental Perspectives;228
1.6.2.5;References;231
1.6.3;Chapter 11: Translating Spermatogonial Stem Cell Transplantation to the Clinic;235
1.6.3.1;11.1 Introduction—Clinical Possibilities for Male Fertility Preservation;236
1.6.3.2;11.2 Primate Spermatogonial Stem Cells;239
1.6.3.3;11.3 Nonhuman Primate Model for Developing SSC Transplantation;240
1.6.3.3.1;11.3.1 SSC Transplantation in Rodents;240
1.6.3.3.2;11.3.2 Primate Testis Cell Isolation;241
1.6.3.3.3;11.3.3 Cryopreservation;242
1.6.3.3.4;11.3.4 Recipient Models for SSC Transplantation;244
1.6.3.3.5;11.3.5 Busulfan Treatment;244
1.6.3.3.6;11.3.6 Testicular Irradiation;246
1.6.3.3.7;11.3.7 Ultrasound-Guided Rete Testis Injection;246
1.6.3.3.8;11.3.8 Definitive Autologous SSC Transplants in Primates;249
1.6.3.3.9;11.3.9 Allogeneic SSC Transplants;249
1.6.3.4;11.4 Clinical Implications and Considerations for SSC Transplantation;251
1.6.3.4.1;11.4.1 Patient Testis Accrual;251
1.6.3.4.2;11.4.2 Testis Cell Isolation in the Clinic;252
1.6.3.4.3;11.4.3 Human SSC Culture;252
1.6.3.4.4;11.4.4 Risk of Reintroducing Malignant Cells During SSCs Transplants;253
1.6.3.4.5;11.4.5 Ethical Considerations;254
1.6.3.5;11.5 Conclusions;256
1.6.3.6;References;256
1.7;Index;262