Stem Cells - From Hype to Real Hope / Edition 1

by Khawaja Husnain Haider, Salim Aziz, MD

Overview

This book is a compilation of the bench experience of leading experts from various research labs involved in the cutting edge area of research. The authors describe the use of stem cells both as part of the combinatorial therapeutic intervention approach and as tools (disease model) during drug development, highlighting the shift from a conventional symptomatic treatment strategy to addressing the root cause of the disease process.

The book is a continuum of the previously published book entitled "Stem Cells: from Drug to Drug Discovery" which was published in 2017.

Product Details

ISBN-13:	9783110586787
Publisher:	De Gruyter
Publication date:	12/17/2018
Pages:	220
Product dimensions:	9.45(w) x 6.69(h) x (d)
Age Range:	18 Years

About the Author

Khawaja Husnain Haider, AlQaseem, Kingdom of Saudi Arabia.

Salim Aziz, Washington, DC, USA

Khawaja Husnain Haider, AlQaseem, Kingdom of Saudi Arabia.

Salim Aziz, Washington, DC, USA

Table of Contents

Preface vii

Contributing authors xv

List of abbreviations xix

1 Induced pluripotent stem-cell-derived cardiomyocytes (iPSC-CMs): novel diagnostic platform Valeria A. Tsvelaya Anna Gam Jenna Aziz Igor R. Efimov 1

1.1 Rationale for the emerging need for IPSC-CMs 1

1.2 Cardiogenesis and iPSC differentiation 2

1.3 Reprogramming limitations and improvements 4

1.4 Disease modeling platform 7

1.5 Drug testing platform 9

1.6 Transplantation of in vitro derived CMs into injured areas 11

1.7 Conclusion and future directions 13

1.8 References 13

2 Preclinical large-animal models of cardiovascular regeneration Keron Navarengom Elisa A. Ferrante Todd E. Rasmussen Manfred Boehm 20

2.1 Introduction 20

2.2 Regenerative strategies for HF 21

2.3 Cardiac regeneration using PSCs 22

2.4 Translational models of HF 25

2.5 Large animal models 26

2.5.1 Dilated cardiomyopathy models 26

2.5.2 Surgical induction of myocardial ischemia or infarction 28

2.6 Assessment of animal models 29

2.7 Conclusions 29

2.8 References 29

3 Cell-free therapy with stem cell secretions: protection, repair, and regeneration of the Injured myocardium Khawaja Husnain Haider Muhammad Aslam 34

3.1 Introduction 34

3.2 The secretome of each stem cell type is unique 35

3.2.1 Paracrine factors and angiogenesis 39

3.2.2 Paracrine factors and cytoprotection 40

3.2.3 Paracrine factors and immunomodulation 42

3.2.4 Paracrine factors and cell migration and homing 44

3.2.5 Paracrine Factors and antifibrosis 46

3.3 Tempering the secretome composition with outside intervention 48

3.3.1 Genetic modification of stem cells 48

3.3.2 Chemical and pharmacological manipulation of cells 51

3.3.3 Physical manipulation of cells 53

3.3.4 Heat shock and Shockwave treatment to precondition stem cells 55

3.3.5 Modification of the ECM 56

3.4 Conclusion and future perspective 57

3.5 References 58

4 Myoblasts provide safe and effective treatments for hereditary muscular dystrophies, cardiomyopathiess type 2 diabetes, solid tumors, and aging Peter K. Law Danlin M. Law Lei Ye Khawaja Husnain Haider Shi Jun Song Ping Lu Jian-Hua Ma Jun Ren 71

4.1 Introduction 72

4.2 Gene therapy in the United States 72

4.3 What constitute genetic diseases? 73

4.4 Two kinds of gene therapies 73

4.4.1 Single gene transduction 73

4.4.2 Single gene transduction deficiencies 75

4.4.3 How does single gene transduction fare? 76

4.5 Human genome therapy 76

4.5.1 Myoblasts are not stem cells 77

4.5.2 World's first human gene therapy 78

4.5.3 HMGT/MTT corrects gene defects in DMD clinical trials 78

4.5.4 HMGT/MTT versus Exondys 51 80

4.5.5 HMGT/MTT in heart disease clinical trials 81

4.5.6 Autonomous cell injection catheter 83

4.5.7 HMGT/MTT corrects gene defects in type 2 diabetes 84

4.5.7.1 Human study 84

4.5.7.2 Animal studies 85

4.5.8 Myoblast implantation inhibits metastasis and tumor growth and induces cancer apoptosis 87

4.5.9 Anti-aging aesthetics 88

4.5.10 Skin cover 89

4.5.11 Body sculpture 91

4.5.12 Anti-aging angiomyogenesis 92

4.6 Conclusion 92

4.7 References 93

5 Stem cells in ophthalmology S. Amer Riazuddin Shahid Y. Khan Muhammad Ali John D. Gottsch 98

5.1 Introduction 98

5.2 Cornea 99

5.2.1 Corneal epithelium 99

5.2.2 Corneal stroma 100

5.2.3 Corneal stromal stem cells 100

5.2.4 Corneal endothelium 101

5.2.5 Corneal endothelial stem cells 101

5.2.6 Conjunctiva 102

5.2.7 Conjunctival stem cells 102

5.3 Iris 103

5.3.1 IPE stem cells 103

5.4 Ciliary body 104

5.4.1 Ciliary epithelial stem cells 104

5.5 Trabecular meshwork 104

5.5.1 TM stem cells 104

5.6 Lens 105

5.6.1 Lens stem cells 105

5.7 Retina 106

5.7.1 Retinal stem cells 106

5.7.2 Retinal pigment epithelial stem cells 106

5.7.3 Retinal Müller stem cells 106

5.8 References 107

6 Stem cells for ocular therapies S. Amer Riazuddin Shahid Y. Khan Muhammad Ali John D. Gottsch 116

6.1 Introduction 116

6.2 Cornea 117

6.2.1 Stem cell-based therapies for corneal epithelium 117

6.2.2 Therapeutic applications of stem cells to corneal stroma 118

6.2.3 Stem cells and corneal endothelium treatment 118

6.3 TM and stem cell therapy 119

6.4 Ocular lens and stem cell treatment 120

6.5 Stem cell-based retinal therapy 120

6.6 References 123

7 Cell therapy for liver regeneration Sheikh Riazuddin Maria Tayyab Baig Azra Mehmood 130

7.1 Introduction 130

7.1.1 Worldwide prevalence of liver diseases 130

7.2 Structure and function of the liver 131

7.3 Liver diseases 131

7.3.1 Progression of liver fibrosis to liver cirrhosis 131

7.3.2 Liver failure 132

7.3.3 Liver failure causes malfunctioning of other organs 132

7.4 Conventional therapies for liver diseases 132

7.5 Cellular therapies for liver diseases 132

7.6 Stem cell therapy for liver diseases 133

7.6.1 Liver stem/progenitor cells 133

7.6.2 MSCs in the therapy of liver diseases 134

7.6.2.1 Bone marrow-derived MSCs 134

7.6.2.2 Adipose (tissue)-derived MSCs 137

7.6.2.3 Umbilical-cord-tissue-derived MSCs 138

7.6.2.4 Umbilical cord blood stem cells 138

7.6.3 A comparison of the various sources of MSCs 138

7.6.4 Clinical promises of MSCs 139

7.6.5 Induced pluripotent stem cells 139

7.7 Liver bioengineering/scaffold-assisted liver regeneration 140

7.8 Future prospects of cellular therapies for the repair of damaged livers 141

7.9 References 141

8 Patient-specific induced pluripotent stem cells for cardiac disease modeling Esra Cagavi Tuba Akgul Caglar Khawaja Husnain Haider Gokce Ilayda Soztekin 146

8.1 Introduction 146

8.2 Methods for electrophysiological analysis 148

8.2.1 Electrocardiogram 149

8.2.2 Patch clamp analysis 150

8.2.3 Multielectrode array (MEA) 151

8.2.4 Impedance and field potential (FP) recorders 151

8.2.5 Voltage-sensitive and Ca²⁺-sensitive dyes 151

8.3 Channelopathies 152

8.3.1 Long QT Syndrome Type-1 (LQTS-1) 152

8.3.2 LQTS-2 158

8.3.3 LQTS-3 (Gain-of-Function of Na⁺ Channel) 161

8.3.4 Srugada syndrome 162

8.3.5 Timothy syndrome (LQTS-8) 163

8.3.6 LQTS-14 164

8.3.7 LQTS-15 164

8.4 Catecholaminergic polymorphic ventricular tachycardia 165

8.5 Conclusion 167

8.6 References 168

9 Role of stem cells on evolution: a hypothesis Newton Howard Abderrahmane Hamlat Julie Dubourg Mahmoud Messerer Eduardo Pasqualini 173

9.1 Introduction 173

9.2 Stem cells and evolution 174

9.3 Evolution stages 176

9.4 Evolution and update of genetic database 176

9.4.1 Evolution of genetic database 176

9.4.2 Role of GSCs in genetic database update 178

9.4.3 Memory box and update of genetic database 179

9.5 Evolution and human emergence 179

9.5.1 Brain evolution 180

9.5.2 Differences between human and mammal brains 181

9.6 Conclusions 183

9.7 References 183

Index 188