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Rob Burgess

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Stem Cells: A Short Course is a comprehensive text for students delving into the rapidly evolving discipline of stem cell research. Comprised of eight chapters, the text addresses all of the major facets and disciplines related to stem cell biology and research. A brief history of stem cell research serves as an introduction, followed by coverage of stem cell fundamentals; chapters then explore embryonic and fetal amniotic stem cells, adult stem cells, nuclear reprogramming, and cancer stem cells. The book concludes with chapters on stem cell applications, including the role of stem cells in drug discovery and therapeutic applications in spinal cord injury, brain damage, neurological and autoimmune disorders, among others. Written by a leader in the field, Stem Cells: A Short Course appeals to both students and instructors alike, appealing to academic enthusiasm for stem cell research and applications.

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Veröffentlichungsjahr: 2015

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STEM CELLS

A Short Course

Rob Burgess

Copyright © 2016 by John Wiley & Sons, Inc. All rights reserved.

Published by John Wiley & Sons, Inc., Hoboken, New Jersey. Published simultaneously in Canada.

No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, scanning, or otherwise, except as permitted under Section 107 or 108 of the 1976 United States Copyright Act, without either the prior written permission of the Publisher, or authorization through payment of the appropriate per-copy fee to the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, (978) 750-8400, fax (978) 750-4470, or on the web at www.copyright.com. Requests to the Publisher for permission should be addressed to the Permissions Department, John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, (201) 748-6011, fax (201) 748-6008, or online at http://www.wiley.com/go/permission.

Limit of Liability/Disclaimer of Warranty: While the publisher and author have used their best efforts in preparing this book, they make no representations or warranties with respect to the accuracy or completeness of the contents of this book and specifically disclaim any implied warranties of merchantability or fitness for a particular purpose. No warranty may be created or extended by sales representatives or written sales materials. The advice and strategies contained herein may not be suitable for your situation. You should consult with a professional where appropriate. Neither the publisher nor author shall be liable for any loss of profit or any other commercial damages, including but not limited to special, incidental, consequential, or other damages.

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Library of Congress Cataloging-in-Publication Data is available.

ISBN: 978-1-118-43919-7

To my wife, Jane, daughter, Zoie, son, Bobby, mother, Lola, and father, Bob

CONTENTS

PREFACE TO THE PROFESSOR

PREFACE TO THE STUDENT

ACKNOWLEDGMENTS

LIST OF CASE STUDIES

LIST OF FOCUS BOXES

CHAPTER 1 A HISTORY OF STEM CELL RESEARCH

EARLY STUDIES

HEMATOPOIETIC STEM CELL DISCOVERY

MOUSE EMBRYONIC STEM CELL DISCOVERY

SUCCESSFUL NEURAL STEM CELL CULTURE

THE DISCOVERY OF CANCER STEM CELLS

HUMAN EMBRYONIC STEM CELL DISCOVERY

STEM CELLS AND CLONING

CORD BLOOD EMBRYONIC-LIKE STEM CELLS—AN ALTERNATIVE TO ES AND ADULT STEM CELLS

BREAKTHROUGH IN SPINAL CORD INJURY REPAIR

THE GENERATION OF IPS CELLS

THE DISCOVERY OF HUMAN AMNIOTIC STEM CELLS

HUMAN EMBRYONIC STEM CELLS GENERATED WITHOUT EMBRYO DESTRUCTION

HUMAN CLONING

MESENCHYMAL STEM CELL-DERIVED HUMAN KNEE CARTILAGE

THE FIRST CLINICAL TRIAL USING HUMAN EMBRYONIC STEM CELLS

MITOCHONDRIAL DNA: A BARRIER TO AUTOLOGOUS CELL THERAPEUTICS

INDUCED PLURIPOTENCY AND THE POTENTIAL TO SAVE ENDANGERED SPECIES

CHAPTER SUMMARY

KEY TERMS

REVIEW QUESTIONS

THOUGHT QUESTION

SUGGESTED READINGS

CHAPTER 2 FUNDAMENTALS OF STEM CELLS

BASIC

IN VITRO

CELL CULTURE—A HISTORICAL PERSPECTIVE

STEM CELL CULTURE—OPTIMAL CONDITIONS AND TECHNIQUES

THE STUDY OF EMBRYONIC DEVELOPMENT

BASIC PROPERTIES OF STEM CELLS

TYPES OF STEM CELLS

THE POTENTIAL OF STEM CELLS IN MEDICINE AND MEDICAL RESEARCH

CHAPTER SUMMARY

KEY TERMS

REVIEW QUESTIONS

THOUGHT QUESTION

SUGGESTED READINGS

CHAPTER 3 EMBRYONIC STEM, FETAL, AND AMNIOTIC STEM CELLS

ES CELLS

EC CELLS

EMBRYONAL GERM CELLS

COMPARING EMBRYONICALLY DERIVED CELLS

FETAL STEM CELLS

CHAPTER SUMMARY

KEY TERMS

REVIEW QUESTIONS

THOUGHT QUESTION

SUGGESTED READING

CHAPTER 4 ADULT STEM CELLS

DISCOVERY AND ORIGIN OF ASCs

BASIC PROPERTIES OF ASCs

EXAMPLES OF ASCs

CHAPTER SUMMARY

KEY TERMS

REVIEW QUESTIONS

THOUGHT QUESTION

SUGGESTED READINGS

CHAPTER 5 NUCLEAR REPROGRAMMING

EXAMPLES OF NUCLEAR REPROGRAMMING IN NATURE

CELL FUSION

SOMATIC CELL NUCLEAR TRANSFER

INDUCED PLURIPOTENCY

ADVANTAGES OF IPS CELLS OVER OTHER CELL TYPES

CHAPTER SUMMARY

KEY TERMS

REVIEW QUESTIONS

THOUGHT QUESTION

SUGGESTED READINGS

CHAPTER 6 CANCER STEM CELLS

BACKGROUND ON THE ORIGINS OF CANCER

DISCOVERY AND ORIGIN OF CANCER STEM CELLS

BASIC PROPERTIES OF CANCER STEM CELLS

SIGNALING PATHWAYS INVOLVED IN CANCER STEM CELL TRANSFORMATION

EXAMPLES OF CANCER STEM CELLS

STRATEGIES FOR TREATMENT TARGETING CANCER STEM CELLS

CHAPTER SUMMARY

KEY TERMS

REVIEW QUESTIONS

THOUGHT QUESTION

SUGGESTED READINGS

CHAPTER 7 STEM CELLS AS DRUG DISCOVERY PLATFORMS

EMBRYONIC STEM CELLS AND MOUSE MODELS OF GENE FUNCTION

STEM CELL-BASED SCREENING ASSAYS

ANALYSIS OF DISEASE PATHWAYS

STEM CELLS AS A TOXICITY-TESTING PLATFORM

CHAPTER SUMMARY

KEY TERMS

REVIEW QUESTIONS

THOUGHT QUESTION

SUGGESTED READINGS

CHAPTER 8 THERAPEUTIC APPLICATIONS OF STEM CELLS

HISTORY OF STEM CELLS AS THERAPEUTICS

DISEASE-SPECIFIC TREATMENT AND PATIENT TRIALS

VETERINARY APPLICATIONS

STEM CELLS AS AN EMERGING INDUSTRY

CHAPTER SUMMARY

KEY TERMS

REVIEW QUESTIONS

THOUGHT QUESTION

SUGGESTED READINGS

ABOUT THE AUTHOR

INDEX

EULA

List of Tables

Chapter 1

Table 1.1

Chapter 2

Table 2.1

Chapter 3

Table 3.1

Table 3.2

Table 3.3

Chapter 4

Table 4.1

Table 4.2

Table 4.3

Table 4.4

Table 4.5

Chapter 5

Table 5.1

Table 5.2

Table 5.3

Chapter 6

Table 6.1

Chapter 7

Table 7.1

Chapter 8

Table 8.1

Table 8.2

List of Illustrations

Chapter 1

Figure 1.1

Timeline of historical advances in stem cell theory and research. (Adapted from Rob Burgess,

Stem Cells Handbook

(Humana Press), 2nd Edition, Chapter 1.)

Figure 1.2

The late Ernest McCulloch and James Till after accepting the 2005 Lasker Award for their studies on bone marrow-derived stem cells.

Ernest McCulloch is at left. (Photograph courtesy Environmental Protection Agency; reprinted with permission.)

Figure 1.3

Discovery of active neurogenesis in the adult brain. The arrows denote

3

H-thymidine uptake in glial cells in rodent brain regions associated with trauma. Neurons and neuroblasts also demonstrated some staining, confirming mitosis and corresponding neurogenesis. (Photo courtesy

Nature

(Altman and Das, 1967); reprinted with permission.)

Figure 1.4

Dr. Robert Alan Goodwith, President Richard Nixon, and colleagues at the White House Conquest of Cancer Program in 1973

. Dr. Goodwith is circled; President Nixon is second from the left. Also pictured is Dr. Robert L. Clark of the University of Texas M.D. Anderson Cancer Center. (Photo courtesy Nixon archives; reprinted with permission.)

Figure 1.5

Hematopoietic stem cells isolated from human umbilical cord blood. (a) Colony cultured on methylcellulose. (b) Myelocytes and metamyelocytes. (c) Neutrophils. (d) Dividing myelocyte. (Photo courtesy Dr. G. Prindull and

Acta Paediatrica Scandinavica

(Prindull and Prindull, 1978); reprinted with permission.)

Figure 1.6

The discovery of mouse embryonic stem cells. (Left) The first published photo documentation of a mouse embryonic stem cell colony. (Right) Embryoid bodies demonstrating a variety of different cell types including (a) giant cells, (b) neuron-like cells, (c) endodermal cells, (d) cartilage, and (e) cells forming tubules. Source: Martin, 1981. Reproduced with permission from G. R. Martin.)

Figure 1.7

Generation and characterization of multipotent neural stem cells. (a) Non-cultured control and (b) 8-day coculture of transformed neural stem cells (stained in blue) with dissociated primary mouse cerebellum demonstrating process formation. (c–e) Sections of the cerebellar region of a mouse brain transplanted with LacZ tagged v-myc transformed neural stem cells. (c) Six hours post transplant; (d and e) 72 hours post transplant demonstrating proper migration into the molecular layer. (Photos courtesy Constance Cepko and

Cell

(Snyder et al., 1992); reprinted with permission.)

Figure 1.8

Differentiation capacity of SL-IC cancer stem cells. (a and c) Unsorted and (b and d)

sorted CD34+/CD38- SL-ICs demonstrating colonization of the bone marrow of a recipient NOD/SCID mouse as assayed by the presence of the marker CD45 which is a transmembrane glycoprotein present on the cell surface of all cells of hematopoietic origin. (Photos courtesy John Dick and

Nature Medicine

(Bonnet and Dick, 1997); reprinted with permission.)

Figure 1.9

Derivation of the 1st clonal human embryonic stem cell line. (a) First inner cell mass colony cultured on a mouse feeder layer. (b) H9 clonal undifferentiated human ES cell colony. (c) High magnification of individual human ES cells. (d) Differentiated human ES cells cultured in the absence of a mouse feeder layer. (Photos courtesy Dr. James A. Thomson and

Science

(Thomson et al., 1998); reprinted with permission.)

Figure 1.10

Diagrammatic illustration of Somatic Cell Nuclear Transfer (SCNT). See text for a detailed description. (Diagram courtesy Wikipedia.org; reprinted with permission.)

Figure 1.11

Diagram of the procedure undertaken for cloning Dolly the sheep. (Diagram courtesy Wikimedia Commons; reprinted with permission.)

Figure 1.12

Advanced Cell Technology’s parthenogenetically activated human embryos. (a)

Isolated

unfertilized eggs. (b) 4–6 cell embryos 48 hours after activation of parthenogenesis. (c) Day 6 revealing blastocoele cavities indicated by arrows. (Photos courtesy Jose B. Cibelli and

Scientific American

(Cibelli et al., 2002); reprinted with permission.)

Figure 1.13

Somatic cell nuclear transfer cumulus cell-derived human embryos. (a)

12 hou

rs, (b) 36 hours (2 cell stage), (c) 72 hours (4-cell stage), and (d) 72 hours (6-cell stage) after nuclear transfer. (c) and (d) indicate nuclei stained with the fluorescent label bisbenzimide. (Photos courtesy Jose B. Cibelli and

Scientific American

(Cibelli et al., 2002); reprinted with permission.)

Figure 1.14

Marker characterization of cord blood embryonic-like stem cells. Cells were positive for the classical ES markers SSEA-3, SSEA-4, Tra 1-60, Tra 1-81 and Oct-4 yet, as is characteristic of embryonic stem cells, the CBEs did not express SSEA-1. (Photos courtesy Colin P. McGuckin and (McGuckin et al., 2005); reprinted with permission.)

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