Stem cells in endocrinology

289 Pages·2005·9.381 MB·English

by  Linda B Lester

CONTEMPORARY ENDOCRINOLOGY™
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ERIES DITOR
Stem Cells in Endocrinology, edited by Assisted Fertilization and Nuclear Transfer
LINDA B. LESTER, 2005 in Mammals, edited by DON P. WOLF
Office Andrology, edited by PHILLIP E. AND MARY ZELINSKI-WOOTEN, 2001
PATTON AND DAVID E. BATTAGLIA, 2005 Adrenal Disorders, edited by ANDREW N.
Male Hypogonadism: Basic, Clinical, and MARGIORIS AND GEORGE P. CHROUSOS,
Therapeutic Principles, edited by 2001
STEPHEN J. WINTERS, 2004 Endocrine Oncology, edited by STEPHEN P.
Androgens in Health and Disease, edited ETHIER, 2000
by CARRIE J. BAGATELL AND WILLIAM J. Endocrinology of the Lung: Development
BREMNER, 2003 and Surfactant Synthesis, edited by
Endocrine Replacement Therapy in Clinical CAROLE R. MENDELSON, 2000
Practice, edited by A. WAYNE MEIKLE, Sports Endocrinology, edited by MICHELLE P.
2003 WARREN AND NAAMA W. CONSTANTINI, 2000
Early Diagnosis of Endocrine Diseases, Gene Engineering in Endocrinology, edited
edited by ROBERT S. BAR, 2003 by MARGARET A. SHUPNIK, 2000
Type I Diabetes: Etiology and Treatment, Endocrinology of Aging, edited by JOHN E.
edited by MARK A. SPERLING, 2003 MORLEY AND LUCRETIA VAN DEN BERG, 2000
Handbook of Diagnostic Endocrinology, Human Growth Hormone: Research and
edited by JANET E. HALL AND LYNNETTE Clinical Practice, edited by ROY G.
K. NIEMAN, 2003 SMITH AND MICHAEL O. THORNER, 2000
Pediatric Endocrinology: A Practical Hormones and the Heart in Health and
Clinical Guide, edited by SALLY Disease, edited by LEONARD SHARE, 1999
RADOVICK AND MARGARET H. Menopause: Endocrinology and Management,
MACGILLIVRAY, 2003 edited by DAVID B. SEIFER AND
Diseases of the Thyroid, 2nd ed., edited by ELIZABETH A. KENNARD, 1999
LEWIS E. BRAVERMAN, 2003 The IGF System: Molecular Biology,
Developmental Endocrinology: From Physiology, and Clinical Applications,
Research to Clinical Practice, edited edited by RON G. ROSENFELD AND
by ERICA A. EUGSTER AND ORA HIRSCH CHARLES T. ROBERTS, JR., 1999
PESCOVITZ, 2002 Neurosteroids: A New Regulatory Function
Osteoporosis: Pathophysiology and Clinical in the Nervous System, edited by
Management, edited by ERIC S. ETIENNE-EMILE BAULIEU, MICHAEL
ORWOLL AND MICHAEL BLIZIOTES, 2002 SCHUMACHER, AND PAUL ROBEL, 1999
Challenging Cases in Endocrinology, Autoimmune Endocrinopathies, edited by
edited by MARK E. MOLITCH, 2002 ROBERT VOLPÉ, 1999
Selective Estrogen Receptor Modulators: Hormone Resistance Syndromes, edited by
Research and Clinical Applications, J. LARRY JAMESON, 1999
edited by ANDREA MANNI AND MICHAEL Hormone Replacement Therapy, edited by
F. VERDERAME, 2002 A. WAYNE MEIKLE, 1999
Transgenics in Endocrinology, edited by Insulin Resistance: The Metabolic Syndrome X,
MARTIN MATZUK, CHESTER W. BROWN, edited by GERALD M. REAVEN AND AMI LAWS,
AND T. RAJENDRA KUMAR, 2001 1999
S C
TEM ELLS
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IN NDOCRINOLOGY
Edited by
L B. L , ,
INDA ESTER MS MD
Division of Endocrinology, Diabetes and Clinical Nutrition
Department of Medicine, Oregon Health and Sciences University
Portland, Oregon
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Library of Congress Cataloging-in-Publication Data
Stem cells in endocrinology / edited by Linda B. Lester.
p. cm. -- (Contemporary endocrinology)
Includes bibliographical references and index.
ISBN 1-58829-407-2 (alk. paper)
1. Stem cells. 2. Endocrinology, Experimental. I. Lester, Linda B. II.
Series: Contemporary endocrinology (Totowa, N.J.)
QH588.S83S747 2005
616'.02774--dc22
2004017508
Dedication
The lights of stars that were extinguished ages ago still reach us.
So it is with great men who died centuries ago, but still reach us
with the radiations of their personalities.
— KHALIL GIBRAN
The recent death of James R. Hansen, MD (August 24, 1951 to May 27, 2003)
cut short a life dedicated to family, patients, and a cure for type 1 diabetes. After
medical school at Oregon Health Sciences University, Jim completed a pediatric
residency and pediatric endocrine fellowship at the University of Iowa. Upon
returning to Portland, Oregon, Jim became medical director of the Emanuel
Children’s Diabetes and Endocrine Center. There he worked passionately to care
for his patients with type 1 diabetes and continued to pursue novel diabetes thera-
pies through ongoing clinical research. Jim was actively involved with the
Juvenile Diabetes Research Foundation (JDRF) at both the local and interna-
tional levels. He was very enthusiastic about the use of stem cells for endocrine
therapies, particularly for treating patients with type 1 diabetes. Jim served as the
committee chair for the JDRF’s Human Stem Cell Research Committee up until
a few weeks before his death.
This book is dedicated to Dr. James Hansen, in memory of his life, vision, and
inspiration. He continues to shine for those of us he touched.
v

Preface
As the world population ages, health care costs are expected to escalate as a
result of the increase in age-related, degenerative diseases. Regenerating the
failing cells and organs associated with these diseases would preserve quality of
life and help curtail the increase in health care costs. Medical scientists today are
faced with the challenge of developing new and innovative regenerative thera-
pies to meet this need. A major focus of this research is to identify sources of cells
and tissues that can be used in regenerative therapies. Stem cells, by definition,
can self-replicate and, under the right conditions, differentiate into mature cell
phenotypes. Stem cells are a potential source of cells for regenerative medical
therapies, and research on defined stem cell populations will facilitate the study
of organ development ex vivo. Understanding stem cell growth and development
will shed light on the biological process of tissue/organ development and likely
lead to novel regenerative therapies.
Although all stem cells have a limited capacity for self-replication and differ-
entiation, some stem cells are capable of differentiating into multiple cell types,
a property known as plasticity. Embryonic stem (ES) cells are derived from the
early blastocyst and contain stem cells capable of generating all adult tissues.
This makes ES cells the most pluripotent, or plastic, of the available stem cells.
Recently, ES cell lines were derived from animal and human blastocysts. These
cell lines are capable of self-replication and can be expanded in culture to provide
a renewable source of cells. Human ES cell lines are an invaluable research tool
for the study of human development in vitro. In addition, human ES cells have
the potential for direct use in therapies; thus, these cell lines represent a major
advance in cell biology that will have a broad impact on subsequent medical
research.
The study of stem cell biology is likely to have profound effects for the near
future, affecting the current equilibrium in medical research. The evolution of
science and medicine is punctuated by events that are clearly so significant that
they alter the future course of scientific and medical discovery. The derivation
of human ES cell lines, in my mind, is clearly such an event. Human ES cell lines,
along with other stem cell lines, will have broad and long-lasting effects on
developmental biology and translational research. However, the fundamental
importance of ES cell lines does not necessarily imply that ES cells will become
vii
viii Preface
the cell source for regenerative medicine. The appropriate stem cells will need
to be evaluated for each disease system that may benefit from regenerative
therapy.
Many disease processes stand to benefit from regenerative medical therapies,
including disorders of the central nervous system, cardiovascular, gastrointestinal,
and hematologic systems. Currently, some of these disorders can be treated using
whole organ transplantation. However, whole organ transplantation is limited to
a small percent of patients because of the scarcity of organs for donation and the
need for broad spectrum immunosuppressive therapies. As opposed to other
systems, degenerative disorders of the endocrine system can currently be treated
using exogenous hormonal therapies. These therapies, however, are frequently
inadequate, resulting in significant morbidity and mortality to patients. The
difficulty in treating endocrine disorders is developing a therapy that mimics the
natural feedback mechanisms inherent to functional endocrine organs. Most current
exogenous endocrine therapies fail to mimic the precise metabolic control of endog-
enous hormone release, resulting in under- or overtreatment and thereby leading
to complications. This is clearly illustrated by the persistent complications of
diabetes in patients on exogenous insulin therapy. Replacing endocrine organ
function with functionally responsive cells will allow for the precise regulation
of hormone release through natural feedback and should dramatically improve
medical care. The recent success of islet transplantation indicates the potential
for cell therapies to improve medical care for patients with diabetes. Again, the
major drawback is the lack of tissue available for these procedures. The shortage
of islets and other endocrine tissues could be overcome by developing alternative
tissue sources such as the use of stem cells. Endocrine diseases, in particular
diabetes, are therefore prime targets for stem cell therapeutics.
The objective of this text is to provide a primary source of information on basic
stem cell biology and the application of stem cell research to endocrine diseases.
As such, this book should be useful for both clinical endocrinologists and endo-
crine researchers alike. The information in this book is divided into two main
sections: first, a basic stem cell biology section and second, translational stem
cell research with endocrine applications. In the basic science section, each of the
major sources of stem cells are discussed, including embryonic, cord blood, germ
line, and adult stem cells tissues. Because it is not clear which stem cell types will
eventually be used for endocrine therapies discussing all stem cells allows a
side-by-side comparison of the different stem cell types and a full understanding
of the pros and cons of each. The second section explores how stem cells may be
employed to develop endocrine-related cells or tissues. This includes discus-
sions on directed differentiation using transgenes and development of endocrine-
specific phenotypes including β-cells, hepatocytes, bone, and sperm. Because
Preface ix
many endocrine disorders are autoimmune mediated, we also include a discus-
sion of stem cell therapy for the treatment of autoimmune disorders. In the future,
stem cell therapies for thyroid and other endocrine disorders may be available,
but these areas are not discussed given the limited amount of research currently
available.
In closing, I would like to thank all the contributing authors for taking time
from their research efforts to share their thoughts and ideas in this book. Their
collective expertise provides an excellent starting point for the endocrine
researcher, illuminating the complexity and potential of stem cell research in
endocrinology. I also want to thank Drs. Laura Andrews and Brian Nauert for
their thoughts, editorial comments, and efforts in my research lab while I was
working on this project. Finally, I would like to thank Dr. Lynn Loriaux for his
ongoing support of stem cell research at Oregon Health and Sciences University
and my family, for enduring cold dinners and late nights with few complaints. I
could not flourish without their support and encouragement. My accomplish-
ments are clearly a reflection of all those around me.
Linda B. Lester, MS, MD