Clinical Regenerative Medicine in Urology

 

Description:

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:

 

Part I: Introduction

1: Current Developments and Future Perspectives of Tissue Engineering and Regenerative Medicine

1.1 Introduction

1.2 Current Developments in TERM

1.2.1 Cell Source

1.2.2 Biomaterials

1.2.3 Vascularization

1.2.4 Bioreactors

1.2.5 New and Innovative Technologies for TERM Applications

1.3 Challenges and Future Perspectives

References

Part II: Fundamentals of Regenerative Medicine

2: Biomaterials and Tissue Engineering

2.1 Introduction

2.2 Types of Biomaterials

2.2.1 Natural Polymers

2.2.2 Acellular Tissue Matrices

2.2.3 Synthetic Biodegradable Polymers

2.3 Basic Requirements of Biomaterials in Tissue Engineering

2.3.1 Scaffolding System: Template

2.3.2 Biodegradability/Bioabsorbability

2.4 Advanced Biomaterial Systems in Tissue Engineering

2.4.1 Surface Modification

2.4.2 Drug Delivery System

2.4.3 ECM-Mimetic Biomaterials

2.4.4 Biophysical Signals

2.5 Scaffold Fabrication Technologies

2.5.1 Hydrogels

2.5.2 Electrospinning

2.5.3 Computer-Aided Scaffold Fabrication

2.6 Tissue Engineering Applications

2.6.1 Bulking Agents for Urinary Incontinence and Vesicoureteral Reflux

2.6.2 Injection Therapy Using Muscle Progenitor Cells

2.6.3 Endocrine Replacement

2.6.4 Urethral Tissue

2.6.5 Bladder

2.6.6 Male and Female Reproductive Organs

2.6.7 Kidney

2.6.8 Blood Vessels

2.6.9 Skeletal Muscle and Innervation

2.7 Vascularization of Engineered Tissues

2.7.1 Angiogenic Factor Delivery

2.7.2 Incorporation of Endothelial Cells

2.8 Conclusions and Future Directions

References

3: Cell Technologies

3.1 Available Stem Cell Types for Urology Field

3.1.1 Overview

3.1.2 Stem Cell Properties

3.1.3 Similarities and Differences Between Embryonic and Adult Stem Cells

3.1.3.1 Embryonic Stem Cells, ES Cells

Pluripotency

ES Cell Markers

Proliferation and Differentiation

Stemness Maintenances

Potential Clinical use

Application to Genetic Disorders

Repair of DNA Damage

Preparation Method for hES Cells

Difficulties

3.1.3.2 Reprogrammed Stem Cells

Cell Sources for Reprogramming

Classification by Potency

iPSC Strategy

Reprogramming Factors

Rejuvenation Mechanism

Immune Response

Teratoma Formation Mechanism

3.1.3.3 Reprogramming Methods

Somatic Cell Nuclear Transfer

Induced Totipotent Cells without SCNT

Reprogramming with Reagents

Single Transcription Factor

CRISPR-Mediated Activator

Antibody-Based Reprogramming

Conditionally Reprogrammed Cells

Lineage-Specific Enhancers

Indirect Lineage Conversion

Outer Membrane Glycoprotein

Physical Approach

3.1.3.4 iPSCs Generate Systems

Viral System

miRNA System

Chemical Compound System

Kinase Inhibitor System

Plasmid System

Episome System

Lipofectamine System

3.1.3.5 Mesenchymal Stem Cells, MSCs

Morphology

Cell Sources

Identification Markers

Differentiation Capacity

Immunomodulatory Effects

Homogenous Isolation

3.1.3.6 Cord Blood and Amniotic Fluid-Derived Stem Cells

Cord Blood Stem Cells

Amniotic Stem Cells [48]

3.2 Applications

3.2.1 Stem Cell Culture

3.2.1.1 Human Embryonic Stem Cell Culture Protocol

Isolation of Primary Mouse Embryo Fibroblasts

Preparation of MEF-Conditioned Medium, MEF-CM

Microdissection Passaging of hESCs

3.2.1.2 Human-Induced Pluripotent Stem Cell Generation Protocol

Preparation of Fibroblasts

Lentivirus Production

Lentiviral Infection

Preparation of SNL Feeder Cells

Preparation of Plat-E Cells

Generation of iPS Cells

3.2.1.3 Mesenchymal Stem Cell Culture Protocol

Mesenchymal Stem Cell Isolation from Human Amniotic Membrane

Mesenchymal Stem Cell Isolation from Adipose Tissue

Mesenchymal Stem Cell Isolation from Cord Blood

Mesenchymal Stem Cell Isolation from Amniotic Fluid

Mesenchymal Stem Cell Isolation from Mouse Bone Marrow

Mesenchymal Stem Cells Isolated from Peripheral Blood

3.2.2 Stem Cell Characteristic Analysis Methods

3.2.2.1 Culture-Related Factors

Possible Changes

Colony-Forming Unit-Fibroblastic (CFU-F)

Karyotyping

Fluorescence In Situ Hybridization (FISH)

Comparative Genomic Hybridization

SNP Analysis

Epigenetic Profiling

Flow Cytometry

Immunocytochemistry and Immunohistochemistry

RT-PCR, RT-qPCR, and Digital PCR

Western Blotting

Biomarker Analysis

Embryoid Body and Teratoma Formation

3.2.3 Cellular Differentiation Mechanisms

3.2.3.1 Epigenetics in Stem Cell Differentiation

Epigenetic Control

Mechanisms of Epigenetic Regulation

Cell Signaling in Epigenetic Control

Matrix Elasticity Effect on Differentiation

3.2.4 Stem Cell Therapy and Research

3.2.4.1 Transplantation of Stem Cells

3.2.4.2 For Research

3.2.4.3 For Disease

3.2.4.4 For Drug Discovery

3.2.4.5 Clinical Translation

3.2.4.6 Challenges

3.2.4.7 Conservation

References

4: Bioreactors for Regenerative Medicine in Urology

4.1 Introduction

4.2 Fundamental Design and Types of Bioreactor Systems

4.2.1 Spinner Flask Bioreactor System

4.2.2 Rotating Wall Vessel (RWV) Bioreactor System

4.2.3 Hollow Fiber System

4.2.4 Hollow Fiber-Incorporated Perfusion Bioreactor

4.3 Application of Bioreactors for the Engineering of Urogenital Constructs

4.3.1 Bladder

4.3.2 Urethra and Ureter

4.3.3 Kidney

4.4 Future Perspectives

References

5: 3D Bioprinting for Tissue Engineering

5.1 Introduction

5.2 Bioprinting Techniques

5.2.1 Jetting-Based Bioprinting

5.2.2 Extrusion-Based Bioprinting

5.2.3 Laser-Based Bioprinting (LBB)

5.2.3.1 Stereolithography (SLA)

5.2.3.2 Laser-Assisted Bioprinting (LAB)

5.3 Applications

5.3.1 Tissue Engineering

5.3.1.1 Blood Vessels

5.3.1.2 Bone and Cartilage

5.3.1.3 Other Organs

5.3.2 Bio-Chip

5.3.2.1 Body-on-a-Chip

5.3.2.2 Biosensor

5.3.3 Drug Delivery System

References

6: Decellularization

6.1 Introduction

6.2 Rationale for Decellularization

6.3 Decellularization Protocols

6.3.1 Physical Methods

6.3.1.1 Temperature

6.3.1.2 Force and Pressure

6.3.2 Chemical Methods

6.3.2.1 Acids and Bases

6.3.2.2 Hypotonic and Hypertonic Solutions

6.3.2.3 Detergents

6.3.2.4 Alcohols

6.3.3 Biologic Agents

6.3.3.1 Enzymes

6.3.3.2 Nonenzymatic Agents

6.4 Changes in the Mechanical Properties of Decellularized ECM During Constructive Remodeling

6.5 Sterilization of Decellularized Scaffolds

6.5.1 Ethylene Oxide Exposure

6.5.2 Gamma Irradiation Exposure

6.5.3 Supercritical Carbon Dioxide

6.6 Effects and Evaluation of Decellularized Scaffolds

6.7 Removal of Residual Chemicals

6.8 Eight Decellularized Scaffolds as a Platform for Bioengineered Organs

6.8.1 Liver

6.8.2 Heart

6.8.3 Lung

6.8.4 Kidney

6.8.5 Pancreas

6.8.6 Spinal Cord and Brain

6.8.7 Visceral Organs

6.8.8 Skin

References

Part III: Cell and Tissue Applications

7: Kidney

7.1 Introduction

7.2 Mechanisms of Kidney Regeneration

7.2.1 Cells Involved in Kidney Repair

7.2.1.1 Renal Progenitor Cells

7.2.1.2 Proliferation of Mature Renal Epithelial Cells

7.2.1.3 Mesenchymal Stem Cells

7.2.2 Renotropic Factors

7.2.3 Macrophage

7.2.4 Signaling Pathways in Mediating the Regenerative Process

7.2.4.1 PI3K/AKT/mTOR Pathway

7.2.4.2 Wnt/GSK3/β-Catenin Pathway

7.2.4.3 JAK/STAT Pathway

7.2.4.4 MAPK/ERK Pathway

7.3 Improving Renal Function After Kidney Injury

7.3.1 Cell-Based Approach

7.3.2 Developmental Biology

7.4 De Novo Organ Regeneration

7.4.1 Artificial Scaffold

7.4.1.1 Bioengineered Scaffold

7.4.1.2 Decellularized Cadaveric Scaffold

7.4.2 Isolation of Cells

7.4.2.1 Label-Retaining Cells

7.4.2.2 Side Population Cells

7.4.2.3 Cell Surface Markers

7.4.2.4 Cell Culture

7.4.2.5 Parietal Epithelial Cells

7.4.3 Potential Cell Sources for Renal Regeneration

7.4.3.1 Kidney Tissue-Derived Cells

Primary Kidney Cells

Renal Stem/Progenitor Cells

7.4.3.2 Mesenchymal Stem Cells

Bone Marrow-Derived Stem Cells

Adipose Tissue-Derived Stem Cells

Umbilical Cord Blood-Derived Stem Cells

Amniotic Fluid Stem Cells

Endothelial Progenitor Cells

7.4.3.3 Pluripotent Stem Cell

Embryonic Stem Cell

Induced Pluripotent Stem Cell

7.4.4 In Vitro Kidney Regeneration Without Scaffolds

7.4.5 Blastocyst Complementation

7.4.6 Embryonic Organ Transplantation

7.4.7 Renal Tissue Regeneration Using Metanephric Progenitor Cells

7.4.8 Kidney Regeneration Using Xenoembryos

7.5 Bioartificial Kidney

7.5.1 Renal Tubule Assist Device

7.5.2 Bioartificial Renal Epithelial Cell System

7.5.3 Wearable or Implantable Bioartificial Kidney

7.6 Future Perspectives

References

8: Bladder

8.1 Introduction

8.2 The Use of Matrices for Bladder Regeneration

8.2.1 Naturally Derived Matrices

8.2.2 Synthetic Matrices

8.2.3 Acellular Tissue Matrices

8.2.4 Hybrid or Composite Scaffolds

8.3 Bladder Regeneration Using Cell Transplantation

8.3.1 Mesenchymal Stem Cell

8.3.2 Embryonic Stem Cell

8.3.3 Urine-Derived Stem Cell

8.3.4 Induced Pluripotent Stem Cell

8.4 Tissue Engineering Approach for Bladder Regeneration

8.4.1 Animal Models

8.4.2 Human Models

8.4.3 Neo-urinary Conduits

8.4.4 Kyungpook National University Experiences

8.4.5 Whole Bladder Reconstruction

8.5 Conclusions and Perspectives

References

9: Urethra

9.1 Introduction

9.2 Tissue Engineering for Urethroplasty to Treat Urethral Lesions

9.2.1 Natural Materials

9.2.2 Synthetic Polymers

9.2.3 Hybrid or Composite Scaffolds

9.2.3.1 Acellular Matrices Utilized in Animal Models

9.2.3.2 Acellular Matrices Utilized in Human Models

9.2.3.3 Cellularized Matrices Utilized in Animal Models (Monoculture)

9.2.3.4 Cellularized Matrices Utilized in Human Models (Monoculture)

9.2.3.5 Recellularized Matrices Utilized in Animal Models (Co-Culture)

9.2.3.6 Recellularized Matrices Utilized in Human Models (Co-Culture)

9.3 Current Challenges and Future Perspectives

References

10: Urethral Sphincter: Stress Urinary Incontinence

10.1 Introduction

10.1.1 Stress Urinary Incontinence

10.1.1.1 Introduction of Stress Urinary Incontinence Including Symptoms

10.1.1.2 Definition of Stress Urinary Incontinence

10.1.1.3 Prevalence of Stress Urinary Incontinence

10.1.1.4 Etiology of Stress Urinary Incontinence

Male

Female

10.1.1.5 Mechanism of Stress Urinary Incontinence

10.1.1.6 Current Clinical Management of Stress Urinary Incontinence

Male

Female

10.1.1.7 Limitation of Current Therapy

10.1.2 Regenerative Medicine for Stress Urinary Incontinence

10.1.2.1 Purpose of Regenerative Medicine

10.1.2.2 Application of Regenerative Medicine for Stress Urinary Incontinence

10.1.2.3 Purpose of This Chapter

10.2 Body

10.2.1 Regenerative Therapy of Stress Urinary Incontinence As Alternative Approach

10.2.1.1 Overview of Cell Therapy for Stress Urinary Incontinence

10.2.1.2 Source of Stem Cells for Stress Urinary Incontinence Therapy

Embryonic Stem Cells

Amniotic Fluid Stem Cells

Induced Pluripotent Stem Cells

Adult Stem Cells

Mesenchymal Stem Cells

Urine-Derived Stem Cells

10.2.1.3 Stem Cell Procurement

10.2.1.4 Stem Cell Homing

10.2.1.5 Stem Cell Differentiation

10.2.1.6 Bioactive Effects of Stem Cells

10.2.2 Experimental Trials

10.2.2.1 Animal Model

10.2.2.2 Pathophysiological Animal Models of Reversible Incontinence

Vaginal Distension Model

Murine Vaginal Distension Model

Cell Therapy in Vaginal Distension Murine Model

Cell Therapy in Vaginal Distension Larger Animal Model

Pudendal Nerve Crush

Pudendal Nerve Crush Model Introduction

Fecal Incontinence

Vaginal Distension Combined with Pudendal Nerve Crush Model

Conclusion of Reversible Incontinence Model

10.2.2.3 Pathophysiological Animal Models of Durable Incontinence

Durable Animal Model

Urethrolysis

First Study of Urethrolysis and Method Including Durability

Limitation of Urethrolysis

Enhanced Model of Urethrolysis (Urethrolysis with Cardiotoxin Injection)

Electrocauterization

Method of Electrocauterization and Durability

Limitation of Electrocauterization

Electrocauterization Studies

Urethral Sphincterotomy

Method of Sphincterotomy and Durability

Limitation of Sphincterotomy

Pubourethral Ligament and Pudendal Nerve Transection

Durability of Pubourethral Ligament and Pudendal Nerve Transection

Bilateral Pudendal Nerve Transection (Transection of the Pudendal Nerve)

Durability of Bilateral Transection of the Pudendal Nerve

Advantage of Transection of the Pudendal Nerve

Limitation of Transection of the Pudendal Nerve

10.2.2.4 Regeneration of the Urethral Sphincter Using Cell Therapy in Animal Models

Mesenchymal Stem Cell-Based Study

Mesenchymal Stem Cell Homing Study

Mesenchymal Stem Cells + Periurethral Injection

Amniotic Fluid Stem Cells

Limitation

Adipose-Derived Stem Cell-Based Study

Adipose-Derived Stem Cell Introduction (Advantage and Disadvantage)

Adipose-Derived Stem Cell Several Studies

Innervation Comment

Muscle-Derived Cells and Muscle-Derived Stem Cell-Based Study

MDS Researches

Muscular Precursor Cell-Based Study

Myoblast Researches

Muscle Precursor Cell Researches

Human Cell-Based Study

Human Muscle Precursor Cell Studies

Human-Human Umbilical Cord Blood Studies

Human Amniotic Fluid Stem Cell Studies

Human Myoblast Studies

10.2.3 Clinical Trials

10.2.3.1 Overview of Clinical Trials

Cell Type on Clinical Trials

Cell Status (Number, Injection Routes, Duration) on Clinical Trials

Overall Outcomes Including Efficacy and Safety on Clinical Trials

Regarding Usage of Bulking Agents

10.2.3.2 First Clinical Trial Using Myoblast and Fibroblast

10.2.3.3 Muscle-Derived Stem Cells and Muscle-Derived Cell Clinical Trial

Muscle-Derived Stem Cell Trials

Limitation of Muscle-Derived Stem Cell Trial

Muscle-Derived Cell Trial and Limitation

Myoblast Trial

Minced Skeletal Muscle Tissue (MSMT)

10.2.3.4 Adipose-Derived Stem Cell Trial

10.2.3.5 Umbilical Cord Blood Mononuclear Cell Trial

10.2.3.6 Total Nucleated Cells with Platelet-Rich Plasma Trial

10.2.3.7 Analysis of Clinical Outcomes and Adverse Events of Cell-Based Therapy in Urinary Inco

Summary and Limitation of Clinical Trials

Discussion/Approach of Clinical Trials

Limitations of (Pre-) Clinical Trials

Limitations of Mesenchymal Stem Cells

10.3 Conclusion

10.3.1 Summary

10.3.2 Future Perspectives

10.3.2.1 Optimization of In Vivo Animal Models

Outline of Animal Models for Cell Therapy

Various Animal Models and Limitation of Small or Large Animal Model

Canine Model

Pig Model

Monkey Model

10.3.2.2 The Adequate Cell Type Needed for Regeneration of Tissue

10.3.2.3 Subtyping the Stress Urinary Incontinence Population

10.3.2.4 Are There Alternatives to Cells?

References

11: Penis and Testis

11.1 Penis

11.1.1 Introduction

11.1.2 Anatomy

11.1.3 Hemodynamics and Mechanism of Erection and Detumescence

11.1.4 Penile Reconstruction

11.1.4.1 Penile Enhancement

11.1.4.2 Tunica Albuginea Reconstruction

11.2 Testis

11.2.1 Introduction

11.2.2 Anatomy

11.2.3 Transplantation of Testicular Tissue

11.2.4 Testosterone Delivery System

 

An aparitie	2 Oct. 2017
Autor	Bup Wan Kim
Dimensiuni	19.28 x 2.13 x 26.49 cm
Editura	Springer
Format	Hardcover
ISBN	9789811027222
Limba	Engleza
Nr pag	292