Clinical Regenerative Medicine In Urology

Description

Clinical Regenerative Medicine in Urology

This multidisciplinary book provides up-to-date information on clinical approaches that combine stem or progenitor cells, biomaterials and scaffolds, growth factors, and other bioactive agents in order to offer improved treatment of urologic disorders including lower urinary tract dysfunction, urinary incontinence, neurogenic bladder, and erectile dysfunction. In providing clinicians and researchers with a broad perspective on the development of regenerative medicine technologies, it will assist in the dissemination of both regenerative medicine principles and a variety of exciting therapeutic options. After an opening section addressing current developments and future perspectives in tissue engineering and regenerative medicine, fundamentals such as cell technologies, biomaterials, bioreactors, bioprinting, and decellularization are covered in detail. The remainder of the book is devoted to the description and evaluation of a range of cell and tissue applications, with individual chapters focusing on the kidney, bladder, urethra, urethral sphincter, and penis and testis.

Table of Contents

1.  Preface
2. Contents
3. Part I: Introduction
   1. Current Developments and Future Perspectives of Tissue Engineering and Regenerative Medicine
   2. Introduction
   3. Current Developments in TERM
   4. Cell Source
   5. Biomaterials
   6. Vascularization
   7. Bioreactors
   8. New and Innovative Technologies for TERM Applications
   9. Challenges and Future Perspectives
   10. References
4. Part II: Fundamentals of Regenerative Medicine
   1. Biomaterials and Tissue Engineering
   2. Introduction
   3. Types of Biomaterials
   4. Natural Polymers
   5. Acellular Tissue Matrices
   6. Synthetic Biodegradable Polymers
   7. Basic Requirements of Biomaterials in Tissue Engineering
   8. Scaffolding System: Template
   9. Biodegradability/Bioabsorbability
   10. Advanced Biomaterial Systems in Tissue Engineering
   11. Surface Modification
   12. Drug Delivery System
   13. ECM-Mimetic Biomaterials
   14. Biophysical Signals
   15. Scaffold Fabrication Technologies
   16. Hydrogels
   17. Electrospinning
   18. Computer-Aided Scaffold Fabrication
   19. Tissue Engineering Applications
   20. Bulking Agents for Urinary Incontinence and Vesicoureteral Reflux
   21. Injection Therapy Using Muscle Progenitor Cells
   22. Endocrine Replacement
   23. Urethral Tissue
   24. Bladder
   25. Male and Female Reproductive Organs
   26. Kidney
   27. Blood Vessels
   28. Skeletal Muscle and Innervation
   29. Vascularization of Engineered Tissues
   30. Angiogenic Factor Delivery
   31. Incorporation of Endothelial Cells
   32. Conclusions and Future Directions
   33. References
   34. Cell Technologies
   35. Available Stem Cell Types for Urology Field
   36. Overview
   37. Stem Cell Properties
   38. Similarities and Differences Between Embryonic and Adult Stem Cells
   39. Embryonic Stem Cells, ES Cells
   40. Pluripotency
   41. ES Cell Markers
   42. Proliferation and Differentiation
   43. Stemness Maintenances
   44. Potential Clinical use
   45. Application to Genetic Disorders
   46. Repair of DNA Damage
   47. Preparation Method for hES Cells
   48. Difficulties
   49. Reprogrammed Stem Cells
   50. Cell Sources for Reprogramming
   51. Classification by Potency
   52. iPSC Strategy
   53. Reprogramming Factors
   54. Rejuvenation Mechanism
   55. Immune Response
   56. Teratoma Formation Mechanism
   57. Reprogramming Methods
   58. Somatic Cell Nuclear Transfer
   59. Induced Totipotent Cells without SCNT
   60. Reprogramming with Reagents
   61. Single Transcription Factor
   62. CRISPR-Mediated Activator
   63. Antibody-Based Reprogramming
   64. Conditionally Reprogrammed Cells
   65. Lineage-Specific Enhancers
   66. Indirect Lineage Conversion
   67. Outer Membrane Glycoprotein
   68. Physical Approach
   69. iPSCs Generate Systems
   70. Viral System
   71. miRNA System
   72. Chemical Compound System
   73. Kinase Inhibitor System
   74. Plasmid System
   75. Episome System
   76. Lipofectamine System
   77. Mesenchymal Stem Cells, MSCs
   78. Morphology
   79. Cell Sources
   80. Identification Markers
   81. Differentiation Capacity
   82. Immunomodulatory Effects
   83. Homogenous Isolation
   84. Cord Blood and Amniotic Fluid-Derived Stem Cells
   85. Cord Blood Stem Cells
   86. Amniotic Stem Cells [48]
   87. Applications
   88. Stem Cell Culture
   89. Human Embryonic Stem Cell Culture Protocol
   90. Isolation of Primary Mouse Embryo Fibroblasts
   91. Preparation of MEF-Conditioned Medium, MEF-CM
   92. Microdissection Passaging of hESCs
   93. Human-Induced Pluripotent Stem Cell Generation Protocol
   94. Preparation of Fibroblasts
   95. Lentivirus Production
   96. Lentiviral Infection
   97. Preparation of SNL Feeder Cells
   98. Preparation of Plat-E Cells
   99. Generation of iPS Cells
   100. 3.2.1.3 Mesenchymal Stem Cell Culture Protocol
   101. Mesenchymal Stem Cell Isolation from Human Amniotic Membrane
   102. Mesenchymal Stem Cell Isolation from Adipose Tissue
   103. Mesenchymal Stem Cell Isolation from Cord Blood
   104. Mesenchymal Stem Cell Isolation from Amniotic Fluid
   105. Mesenchymal Stem Cell Isolation from Mouse Bone Marrow
   106. Mesenchymal Stem Cells Isolated from Peripheral Blood
   107. Stem Cell Characteristic Analysis Methods
   108. Culture-Related Factors
   109. Possible Changes
   110. Colony-Forming Unit-Fibroblastic (CFU-F)
   111. Karyotyping
   112. Fluorescence In Situ Hybridization (FISH)
   113. Comparative Genomic Hybridization
   114. SNP Analysis
   115. Epigenetic Profiling
   116. Flow Cytometry
   117. Immunocytochemistry and Immunohistochemistry
   118. RT-PCR, RT-qPCR, and Digital PCR
   119. Western Blotting
   120. Biomarker Analysis
   121. Embryoid Body and Teratoma Formation
   122. Cellular Differentiation Mechanisms
   123. Epigenetics in Stem Cell Differentiation
   124. Epigenetic Control
   125. Mechanisms of Epigenetic Regulation
   126. Cell Signaling in Epigenetic Control
   127. Matrix Elasticity Effect on Differentiation
   128. Stem Cell Therapy and Research
   129. Transplantation of Stem Cells
   130. For Research
   131. For Disease
   132. For Drug Discovery
   133. Clinical Translation
   134. Challenges
   135. Conservation
   136. References
   137. Bioreactors for Regenerative Medicine in Urology
   138. Introduction
   139. Fundamental Design and Types of Bioreactor Systems
   140. Spinner Flask Bioreactor System
   141. Rotating Wall Vessel (RWV) Bioreactor System
   142. Hollow Fiber System
   143. Hollow Fiber-Incorporated Perfusion Bioreactor
   144. Application of Bioreactors for the Engineering of Urogenital Constructs
   145. Bladder
   146. Urethra and Ureter
   147. Kidney
   148. Future Perspectives
   149. References
   150. 3D Bioprinting for Tissue Engineering
   151. Introduction
   152. Bioprinting Techniques
   153. Jetting-Based Bioprinting
   154. Extrusion-Based Bioprinting
   155. Laser-Based Bioprinting (LBB)
   156. Stereolithography (SLA)
   157. Laser-Assisted Bioprinting (LAB)
   158. Applications
   159. Tissue Engineering
   160. Blood Vessels
   161. Bone and Cartilage
   162. Other Organs
   163. Bio-Chip
   164. Body-on-a-Chip
   165. Biosensor
   166. Drug Delivery System
   167. References
   168. Decellularization
   169. Introduction
   170. Rationale for Decellularization
   171. Decellularization Protocols
   172. Physical Methods
   173. Temperature
   174. Force and Pressure
   175. Chemical Methods
   176. Acids and Bases
   177. Hypotonic and Hypertonic Solutions
   178. Detergents
   179. Alcohols
   180. Biologic Agents
   181. Enzymes
   182. Nonenzymatic Agents
   183. Changes in the Mechanical Properties of Decellularized ECM During Constructive Remodeling
   184. Sterilization of Decellularized Scaffolds
   185. Ethylene Oxide Exposure
   186. Gamma Irradiation Exposure
   187. Supercritical Carbon Dioxide
   188. Effects and Evaluation of Decellularized Scaffolds
   189. Removal of Residual Chemicals
   190. Eight Decellularized Scaffolds as a Platform for Bioengineered Organs
   191. Liver
   192. Heart
   193. Lung
   194. Kidney
   195. Pancreas
   196. Spinal Cord and Brain
   197. Visceral Organs
   198. Skin
   199. References
5. Part III: Cell and Tissue Applications
   1. Kidney
   2. Introduction
   3. Mechanisms of Kidney Regeneration
   4. Cells Involved in Kidney Repair
   5. Renal Progenitor Cells
   6. Proliferation of Mature Renal Epithelial Cells
   7. Mesenchymal Stem Cells
   8. Renotropic Factors
   9. Macrophage
   10. gnaling Pathways in Mediating the Regenerative Process
   11. PI3K/AKT/mTOR Pathway
   12. Wnt/GSK3/β-Catenin Pathway
   13. JAK/STAT Pathway
   14. MAPK/ERK Pathway
   15. Improving Renal Function After Kidney Injury
   16. Cell-Based Approach
   17. Developmental Biology
   18. De Novo Organ Regeneration
   19. Artificial Scaffold
   20. Bioengineered Scaffold
   21. Decellularized Cadaveric Scaffold
   22. Isolation of Cells
   23. Label-Retaining Cells
   24. Side Population Cells
   25. Cell Surface Markers
   26. Cell Culture
   27. Parietal Epithelial Cells
   28. Potential Cell Sources for Renal Regeneration
   29. Kidney Tissue-Derived Cells
   30. Primary Kidney Cells
   31. Renal Stem/Progenitor Cells
   32. Mesenchymal Stem Cells
   33. Bone Marrow-Derived Stem Cells
   34. Adipose Tissue-Derived Stem Cells
   35. Umbilical Cord Blood-Derived Stem Cells
   36. Amniotic Fluid Stem Cells
   37. Endothelial Progenitor Cells
   38. Pluripotent Stem Cell
   39. Embryonic Stem Cell
   40. Induced Pluripotent Stem Cell
   41. In Vitro Kidney Regeneration Without Scaffolds
   42. Blastocyst Complementation
   43. Embryonic Organ Transplantation
   44. Renal Tissue Regeneration Using Metanephric Progenitor Cells
   45. Kidney Regeneration Using Xenoembryos
   46. Bioartificial Kidney
   47. Renal Tubule Assist Device
   48. Bioartificial Renal Epithelial Cell System
   49. Wearable or Implantable Bioartificial Kidney
   50. Future Perspectives
   51. References
   52. Bladder
   53. Introduction
   54. The Use of Matrices for Bladder Regeneration
   55. Naturally Derived Matrices
   56. Synthetic Matrices
   57. Acellular Tissue Matrices
   58. Hybrid or Composite Scaffolds
   59. Bladder Regeneration Using Cell Transplantation
   60. Mesenchymal Stem Cell
   61. Embryonic Stem Cell
   62. Urine-Derived Stem Cell
   63. Induced Pluripotent Stem Cell
   64. Tissue Engineering Approach for Bladder Regeneration
   65. Animal Models
   66. Human Models
   67. Neo-urinary Conduits
   68. Kyungpook National University Experiences
   69. Whole Bladder Reconstruction
   70. Conclusions and Perspectives
   71. References
   72. Urethra
   73. Introduction
   74. Tissue Engineering for Urethroplasty to Treat Urethral Lesions
   75. Natural Materials
   76. Synthetic Polymers
   77. Hybrid or Composite Scaffolds
   78. Acellular Matrices Utilized in Animal Models
   79. Acellular Matrices Utilized in Human Models
   80. Cellularized Matrices Utilized in Animal Models (Monoculture)
   81. Cellularized Matrices Utilized in Human Models (Monoculture)
   82. Recellularized Matrices Utilized in Animal Models (Co-Culture)
   83. Recellularized Matrices Utilized in Human Models (Co-Culture)
   84. Current Challenges and Future Perspectives
   85. References
   86. Urethral Sphincter: Stress Urinary Incontinence
   87. Introduction
   88. Stress Urinary Incontinence
   89. Introduction of Stress Urinary Incontinence Including Symptoms
   90. Definition of Stress Urinary Incontinence
   91. Prevalence of Stress Urinary Incontinence
   92. Etiology of Stress Urinary Incontinence
   93. Male
   94. Female
   95. Mechanism of Stress Urinary Incontinence
   96. Current Clinical Management of Stress Urinary Incontinence
   97. Male
   98. Female
   99. Limitation of Current Therapy
   100. Regenerative Medicine for Stress Urinary Incontinence
   101. Purpose of Regenerative Medicine
   102. Application of Regenerative Medicine for Stress Urinary Incontinence
   103. Purpose of This Chapter
   104. Body
   105. Regenerative Therapy of Stress Urinary Incontinence As Alternative Approach
   106. Overview of Cell Therapy for Stress Urinary Incontinence
   107. Source of Stem Cells for Stress Urinary Incontinence Therapy
   108. Embryonic Stem Cells
   109. Amniotic Fluid Stem Cells
   110. Induced Pluripotent Stem Cells
   111. Adult Stem Cells
   112. Mesenchymal Stem Cells
   113. Urine-Derived Stem Cells
   114. Stem Cell Procurement
   115. Stem Cell Homing
   116. Stem Cell Differentiation
   117. Bioactive Effects of Stem Cells
   118. Experimental Trials
   119. Animal Model
   120. Pathophysiological Animal Models of Reversible Incontinence
   121. Vaginal Distension Model
   122. Murine Vaginal Distension Model
   123. Cell Therapy in Vaginal Distension Murine Model
   124. Cell Therapy in Vaginal Distension Larger Animal Model
   125. Pudendal Nerve Crush
   126. Pudendal Nerve Crush Model Introduction
   127. Fecal Incontinence
   128. Vaginal Distension Combined with Pudendal Nerve Crush Model
   129. Conclusion of Reversible Incontinence Model
   130. Pathophysiological Animal Models of Durable Incontinence
   131. Durable Animal Model
   132. Urethrolysis
   133. First Study of Urethrolysis and Method Including Durability
   134. Limitation of Urethrolysis
   135. Enhanced Model of Urethrolysis (Urethrolysis with Cardiotoxin Injection)
   136. Electrocauterization
   137. Method of Electrocauterization and Durability
   138. Limitation of Electrocauterization
   139. Electrocauterization Studies
   140. Urethral Sphincterotomy
   141. Method of Sphincterotomy and Durability
   142. Limitation of Sphincterotomy
   143. Pubourethral Ligament and Pudendal Nerve Transection
   144. Durability of Pubourethral Ligament and Pudendal Nerve Transection
   145. Bilateral Pudendal Nerve Transection (Transection of the Pudendal Nerve)
   146. Durability of Bilateral Transection of the Pudendal Nerve
   147. Advantage of Transection of the Pudendal Nerve
   148. Limitation of Transection of the Pudendal Nerve
   149. Regeneration of the Urethral Sphincter Using Cell Therapy in Animal Models
   150. Mesenchymal Stem Cell-Based Study
   151. Mesenchymal Stem Cell Homing Study
   152. Mesenchymal Stem Cells + Periurethral Injection
   153. Amniotic Fluid Stem Cells
   154. Limitation
   155. Adipose-Derived Stem Cell-Based Study
   156. Adipose-Derived Stem Cell Introduction (Advantage and Disadvantage)
   157. Adipose-Derived Stem Cell Several Studies
   158. Innervation Comment
   159. Muscle-Derived Cells and Muscle-Derived Stem Cell-Based Study
   160. MDS Researches
   161. Muscular Precursor Cell-Based Study
   162. Myoblast Researches
   163. Muscle Precursor Cell Researches
   164. Human Cell-Based Study
   165. Human Muscle Precursor Cell Studies
   166. Human-Human Umbilical Cord Blood Studies
   167. Human Amniotic Fluid Stem Cell Studies
   168. Human Myoblast Studies
   169. Clinical Trials
   170. Overview of Clinical Trials
   171. Cell Type on Clinical Trials
   172. Cell Status (Number, Injection Routes, Duration) on Clinical Trials
   173. Overall Outcomes Including Efficacy and Safety on Clinical Trials
   174. Regarding Usage of Bulking Agents
   175. First Clinical Trial Using Myoblast and Fibroblast
   176. Muscle-Derived Stem Cells and Muscle-Derived Cell Clinical Trial
   177. Muscle-Derived Stem Cell Trials
   178. Limitation of Muscle-Derived Stem Cell Trial
   179. Muscle-Derived Cell Trial and Limitation
   180. Myoblast Trial
   181. Minced Skeletal Muscle Tissue (MSMT)
   182. Adipose-Derived Stem Cell Trial
   183. Umbilical Cord Blood Mononuclear Cell Trial
   184. Total Nucleated Cells with Platelet-Rich Plasma Trial
   185. Analysis of Clinical Outcomes and Adverse Events of Cell-Based Therapy in Urinary Inco
   186. Summary and Limitation of Clinical Trials
   187. Discussion/Approach of Clinical Trials
   188. Limitations of (Pre-) Clinical Trials
   189. Limitations of Mesenchymal Stem Cells
   190. Conclusion
   191. Summary
   192. Future Perspectives
   193. Optimization of In Vivo Animal Models
   194. Outline of Animal Models for Cell Therapy
   195. Various Animal Models and Limitation of Small or Large Animal Model
   196. Canine Model
   197. Pig Model
   198. Monkey Model
   199. The Adequate Cell Type Needed for Regeneration of Tissue
   200. Subtyping the Stress Urinary Incontinence Population
   201. Are There Alternatives to Cells?
   202. References
   203. Penis and Testis
   204. Penis
   205. Introduction
   206. Anatomy
   207. Hemodynamics and Mechanism of Erection and Detumescence
   208. Penile Reconstruction
   209. Penile Enhancement
   210. Tunica Albuginea Reconstruction
   211. Testis
   212. Introduction
   213. Anatomy
   214. Transplantation of Testicular Tissue
   215. Testosterone Delivery System
   216. References

Editor Biography

Bup Wan Kim, MD, PhDDepartment of Urology, Kyungpook National University HospitalProfessor, Kyungpook National University, College of Medicine