Patient-Specifi Stem Cells

Patient-Specific

Stem Cells

Patient-Specific

Stem Cells

Edited by

Deepak A. Lamba

CRC Press

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v

Contents

Preface.................................................................................................................... vii

About the Editor.....................................................................................................ix

Contributors............................................................................................................xi

1. Human-Induced Pluripotent Stem Cells: Derivation .............................1

Uthra Rajamani, Lindsay Lenaeus, Loren Ornelas, and Dhruv Sareen

2. Human-Induced Pluripotent Stem Cells: Banking

and Characterization....................................................................................23

Uthra Rajamani, Lindsay Lenaeus, Loren Ornelas, and Dhruv Sareen

3. Genetic and Epigenetic Considerations in iPSC Technology ............. 51

Yoshiaki Tanaka and In-Hyun Park

4. CRISPR-Based Genome Engineering in Human Stem Cells..............87

Thelma Garcia and Deepak A. Lamba

5. Stem Cells for Parkinson’s Disease ........................................................ 101

Deepak A. Lamba

6. Huntington’s Disease and Stem Cells.................................................... 115

Karen Ring, Robert O’Brien, Ningzhe Zhang, and Lisa M. Ellerby

7. Applications of Pluripotent Stem Cells in the Therapy

and Modeling of Diabetes and Metabolic Diseases............................ 145

Suranjit Mukherjee and Shuibing Chen

8. Role of iPSCs in Disease Modeling: Gaucher Disease

and Related Disorders ............................................................................... 161

Daniel K. Borger, Elma Aflaki, and Ellen Sidransky

9. Role of Induced Pluripotent Stem Cells in Urological Disease

Modeling and Repair................................................................................. 177

Mohammad Moad, Emma L. Curry, Craig N. Robson, and Rakesh Heer

vi Contents

10. Induced Pluripotent Stem Cells: A Research Tool and a

Potential Therapy for RPE-Associated Blinding Eye Diseases ........ 195

Ruchi Sharma, Balendu Shekhar Jha, and Kapil Bharti

11. Modeling Neuroretinal Development and Disease in Stem Cells.... 231

Deepak A. Lamba

Index .....................................................................................................................253

vii

Preface

One of the biggest challenges faced in medical research has been the creation

of accurate and relevant models of human disease. A number of good animal

models have been developed to understand the pathophysiology. However,

not all of them reflect the human disorder, a classic case being Usher’s syn￾drome, where the mutant mouse does not have the same visual and auditory

defects that patients face. There are others that have been even more difficult

to model due to the multifactorial nature of the condition and due to the lack

of discovery of a single causative gene such as age-related macular degenera￾tion or Alzheimer’s disease. Thus, a more relevant and accurate system will

allow us to make better predictions on relevant therapeutic approaches.

The discovery of human pluripotent stem cells in 1998 followed by the

technological advances to reprogram somatic cells to pluripotent stem cell￾like cells in 2006 has completely revolutionized the way we can now think

about modeling human development and disease. This now coupled with

genome editing technologies such as transcription activator-like effector

nucleases and clustered regularly interspaced short palindromic repeats and

has set us up to develop in vitro models of both two-dimensional and three￾dimensional organoids which can more precisely reflect the disease in the

patients. These combinatorial technologies are already providing us with

better tools and therapeutics in drug discovery or gene therapy.

This book summarizes both the technological advances in the field of the

generation of patient-specific lines and the various gene editing approaches

followed by its applicability in various systems. We hope that the book will

serve as a reference for the current state of the field.

ix

About the Editor

Dr. Deepak A. Lamba earned his medical degree from the University of

Mumbai, Mumbai, India, and practiced as a physician there. He earned a

master’s degree in bioengineering from University of Illinois, in Chicago,

where he worked on a chemically stimulating retinal prosthesis device,

followed by a PhD degree from the University of Washington, in Seattle,

where he focused on generating and transplanting retinal cells derived from

human embryonic stem cells and induced pluripotent stem cells (iPSCs) in

the lab of Dr. Thomas Reh. Dr. Lamba’s research focuses on identifying new

methods to treat degenerative vision disorders, including macular degen￾eration and retinitis pigmentosa, using stem cell technology. His laboratory

is working on two broad areas: (a) feasibility of photoreceptor replacement

therapy and hurdles to successful cellular integration and (b) modeling reti￾nal degenerations in vitro using iPSCs as well as bioengineering and gene

editing technologies.

xi

Contributors

Elma Aflaki

Medical Genetics Branch

National Human Genome Research

Institute

National Institutes of Health

Bethesda, Maryland

Kapil Bharti

Unit on Ocular and Stem Cell

Translational Research

Bethesda, Maryland

Daniel K. Borger

Medical Genetics Branch

National Human Genome Research

Institute

National Institutes of Health

Bethesda, Maryland

Shuibing Chen

Department of Surgery and

Biochemistry

Weill Cornell Medical College

New York, New York

Emma L. Curry

Northern Institute for Cancer

Research

Newcastle University

Newcastle, UK

Lisa M. Ellerby

Buck Institute for Research

on Aging

Novato, California

Thelma Garcia

Buck Institute for Research

on Aging

Novato, California

Rakesh Heer

Northern Institute for Cancer

Research

Newcastle University

Newcastle, UK

Balendu Shekhar Jha

Unit on Ocular and Stem Cell

Translational Research

National Eye Institute

National Institutes of Health

Bethesda, Maryland

Lindsay Lenaeus

Board of Governors Regenerative

Medicine Institute

and

Induced Pluripotent Stem Cell Core

Cedars–Sinai Medical Center

Los Angeles, California

Mohammad Moad

Northern Institute for Cancer

Research

Newcastle University

Newcastle, UK

Suranjit Mukherjee

Department of Surgery

and Biochemistry

Weill Cornell Medical College

New York, New York