Stem Cells: Nuclear Reprogramming and Therapeutic Applications / Edition 1

by Gregory R. Bock, Jamie A. Goode

Overview

Understanding stem cells at the molecular level is essential to understanding their behaviour in a physiological context. This volume in our acclaimed Novartis Foundation series features animated discussion from the world’s experts in this topic on the important ethical issues that are raised by research on stem cells. They review the various regulatory regimes, which apply in different countries – a key factor in determining where future stem cell research is carried out.

Potential clinical applications covered in the book include the production of cardiomyocytes to replace damaged heart tissue, the production of insulin-producing cells for patients with diabetes, and the generation of neurons for the treatment of patients with Parkinson’s disease or spinal cord injury. Particular attention is paid to the factors that maintain stem cells in a pluripotent state or which drive them to create differentiated and lineage-committed cells in vitro and in vivo.  Nuclear reprogramming, the process by which a nucleus acquires developmental potential, is covered here as well. It is relevant to stem cell research generally, and also to research on the cloning of animals by nuclear transfer. 

This book is an essential purchase for all those engaged in stem cell research, whether in the laboratory, the clinic or the regulatory authorities.

From the reviews:

"...this book provides: a comprehensive overview of current issues in stem cell research, with contributions from leading figures..."
—BRITISH SOCIETY OF CELL BIOLOGY

Product Details

ISBN-13:	9780470091432
Publisher:	Wiley
Publication date:	04/22/2005
Series:	Novartis Foundation Symposia , #265
Pages:	230
Product dimensions:	6.08(w) x 9.19(h) x 0.72(d)

About the Author

The Novartis Foundation is an international scientific and educational charity which promotes the study and general knowledge of science and in particular encourages international co-operation in scientific research.

Read an Excerpt

Stem Cells

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John Wiley & Sons

ISBN: 0-470-09143-6

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Chapter One

Chair's introduction

John Gearhart

Department of Gynaecology and Obstetrics, The Johns Hopkins School of Medicine, Baltimore, MD21287, USA

In my introduction I would like to frame some of the questions that we will be addressing over the next several days. Some of these are obvious, but I hope that out of this meeting we will synthesize some new ones.

Clearly, we would like to know what stem cells are, and how we can define them functionally and molecularly. What are their properties? What is this entity known as 'stemness' that has now appeared in the literature? Are we talking about epigenetics or chromatin structure? All of these are likely to be involved. What are the sources of stem cells? In fetal tissues, embryonic tissues, adult tissues, how do we recognize, isolate, characterize and grow them? These are all issues that will be central to our discussions over the next three days. Most importantly, we are concerned about how we can control these cells in the laboratory. How do we get them to do the things that we want them to do, such as differentiating into specific cell types with high efficiency? What strategies are currently used and how successful are these? In grafts, can we get stem cells or their derivatives to do what we want them to do, for example differentiating in a tissue appropriate manner, with no migration and no tumour formation? Also, it is clear that stem cells exist in situ. Will it be possible to manipulate them in situ without taking them out and then grafting them back? Somatic cell nuclear transfer (SCNT, or cell nuclear transfer, CNT) is an important technology in stem cell research. Embryonic stem cells derived from patients will be important in avoiding the immune response to grafted cells and in studying diseases. SCNT will also enable us to study and therefore gain an understanding of the basis of cell differentiation.

Then there is the whole issue of the development of cell-based therapies. While there are some published proofs of principle, there remain many obstacles to developing safe and effective cell-based therapies. Some believe that there should be a more complete understanding of the pathogenesis of the disease and of injuries, so we know exactly what we are doing when we go in and try to replace diseased, injured or dead cells. One area that should receive more attention in the public discussions is the issue of time-frames for the development of safe and effective therapies. We are faced with an issue in the USA of politicians who are elected for 2, 4 or 6 years and want something done within that time-frame. We must be circumspect in making predictions about time-frames. The expectations that go with these predictions or promises that are not met will have serious repercussions. At this meeting we have Tom Murray, who refers to himself as our token ethicist. There are many ethical issues in this field that need to be dealt with fairly. All of us as scientists would feel more comfortable if suitable guidelines were in place. This will come from discussions which not only reflect the sensitivity of the issues, but would also permit robust forward movement of our research. In the USA we see the increasing politicization of the stem cell debate: two members of the President's Council on Bioethics were recently replaced because their views were not in sync with those of the chairman of the Council. We do not know how this will affect recommendations for national policy, but it results in less credibility for the Council.

I am sure that everyone in this room will contribute something significant over the next few days, and we look forward to this mixing of scientists which is at the heart of these symposia.

Many of us have heroes in embryology. One person who stands out for me is Karl Ernst von Baer, and I wanted to reflect on a paraphrase of what he wrote more than 100 years ago: 'All new and truly important ideas and discoveries must pass through three stages: first, dismissed as nonsense, then rejected as against religion, and finally acknowledged as true, with the proviso from initial opponents that they knew it all along.' We are currently between stages two and three.

(Continues...)

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Table of Contents

Chair's Introduction (John Gearhart).

What is a stem cell?  Discussion (Davor Solter).

Bone-marrow derived hepatocytes - Discussion (Markus Grompe).

Normal and neoplastic stem cells - Discussion (Irvin L. Weissman).

Multipotent adult progenitor cells: an update - Discussion (Catherine A. Verfaillie).

Neural progenitor cells of the adult brain - Discussion (Steven A. Goldman and Fraser Sim).

Stem cells in the brain - General Discussion I.

Embryonic stem cells: a perspective - Discussion (Martin Evans).

Nuclear cloning, epigenetic reprogramming and cellular differentiation - Discussion (Rudolf Jaenisch, Konrad Hochedlinger and Kevin Eggan).

General Discussion II.

Nuclear reprogramming by xenopus oocytes - Discussion (J.B. Gordon, J.A. Byrne and S. Simonsson).

Cardiac stem cells and myocardial regeneration - Discussion (Bernardo Nadal-Ginard, Perio Anversa, Jan Kajstura and Annarosa Leri).

Genenration of insulin-producing cells from stem cells - Discussion (Bernat Soria, Enrique Roche, Juan A. Reig and Franz Martin).

Cell therapy for Parkinson's disease: problems and prospects - Discussion (Anders Bjorklund).

Ethical (and political) issues in research with human stem cells - Discussion (Thomas H. Murray).

The regulatory environment - final discussion.

Index of contributors.

Subject index.

Editorial Reviews

Reviewer: Bruce A. Fenderson, PhD (Thomas Jefferson University)
Description: The concept of stem cells seems simple, and yet the biological properties of these amazing cells are complex and many basic questions remain unanswered. For example, we assume that embryonic stem cells are equivalent to cells in the early embryo, but we don't know for sure, and we wonder how these cells are affected by growth in culture. Moreover, the moral and philosophical implications of totipotent stem cells are profound. Many issues are worthy of informed debate. This small book represents the contributions and discussions that took place at a recent Novartis Foundation Symposium in London on the topic of stem cells and nuclear reprogramming. The book includes 14 chapters on topics ranging from "what is a stem cell" to "ethical and political issues in research with human stem cells."
Purpose: According to the chair of this symposium, John Gearhart, the goals were to frame questions important to the field and synthesize some new ones. The evidence for proof-of-principle in cell engineering is critically evaluated. Obstacles to the development of safe and effective cell-based therapies are elaborated. An interesting example of a new question posed by the chair is: "will it be possible to manipulate [stem cells] in situ without taking them out and then grafting them back?"
Audience: The book is written for basic science researchers and clinicians at all levels of training who are interested in embryonic and adult stem cells, and the implications of nuclear reprogramming for tissue engineering. The book provides the reader with access to the inner thinking and honest reflections of many of the world's experts in this exciting field.
Features: This is an excellent introduction to stem cell research. Each chapter includes an abstract and list of essential references. The authors do not present new scientific data; rather, they address general (theoretical) concepts and summarize published literature. For this reason, the book includes very few tables and figures. Early chapters present a summary of information regarding the derivation and properties of stem cells. Evidence for transdifferentiation is debated. Potential problems associated with the lack of differentiation of stem cells following adoptive transfer are discussed. Differences between mouse and human embryonic stem cells are noted. The remarkable ability of egg cytoplasm to reprogram somatic cell nuclei is highlighted. The group discussions are perhaps the most exciting aspect of this book. Fascinating questions arise. For example, are embryonic stem cells immortal? How do you define pleuripotency? What percentage of stem cells in culture is aneuploid? Are there biological differences between embryo-derived and germ cell-derived stem cells? Is it morally acceptable to place human stem cells inside embryos or tissues derived from other species?
Assessment: This compact book is easy to read and the discussions that follow each contribution provide insights into the practice of science as a deeply human enterprise. I learned a great deal. For example, I learned that human and mouse embryonic (ES) cells have different patterns of spontaneous differentiation. Human ES cells transferred into experimental animals often fail to undergo terminal differentiation. Some human ES cell cultures fail to form teratomas in nude mice. The nuclei of differentiated olfactory neurons can be reprogrammed to totipotency by nuclear transfer. Some 20 percent to 80 percent of ES cells in culture are aneuploid. Stem cells with certain karyotypic abnormalities grow faster in culture. The topics are far ranging and thought provoking. I recommend this book for all students interested in learning more about stem cells and prospects for cell-based therapy for chronic diseases like diabetes mellitus, myocardial infarction, and Parkinson's disease.

Doody's Review Service

"...this book provides: a comprehensive overview of current issues in stem cell research, with contributions from leading figures in the field..." (British Society of Cell Biology, January 2006)

"This compact book is easy to read…[discussions] provide insights into the practice of science as a deeply human enterprise. I learned a great deal." (Doody's Health Services)

‘This book is an essential purchase for all those engaged in stem cell research, whether in the laboratory or the clinic.’ (Anticancer Research, 2007)

From the Publisher

5 Stars! from Doody