HJR 588: Medical, Ethical, and Scientific Issues Relating to Stem Cell
Research Conducted in the Commonwealth
September 21, 2005
The September meeting
of the Joint Subcommittee Studying Medical, Ethical, and Scientific Issues
Relating to Stem Cell Research Conducted in the Commonwealth focused on
stem cell research activities in Virginia, particularly at the state's
three medical schools.
VIRGINIA HEALTH SYSTEM PRESENTATION
The first speaker
was Dr. Roy C. Ogle, a Professor of Neurosurgery, Cell Biology and Plastic
Surgery, and the Director of the Center for Human Stem Cell Translational
Research at the University of Virginia School of Medicine. Dr. Ogle's
research interests include investigations of bone repair, including cranial
bone repair with adipose-derived stem cells and regeneration of calvarial
(dome of the cranium) defects with adipose-derived stem cells and multipotent
stem cells from dura mater (the membrane covering the brain and spinal
cord). Dr. Ogle's presentation covered stem cell research, as well as
the use of cell-based therapies.
of Stem Cells
began his presentation by explaining that stem cells can divide and differentiate
into at least one other cell type. After clarifying the common terminology
of embryonic stem cells, fetal stem cells, and adult stem cells, he stressed
that better terminology would be pluripotent stem cells and multipotent
stem cells. Stem cell research, he emphasized, holds promise for drug
development and an improved understanding of gene control.
Dr. Ogle noted that
each type of stem cell has strengths and weaknesses and embryonic and
adult stem cell research are complementary. The strengths of embryonic
stem cells are that they are pluripotent-capable of differentiating into
any cell type and have infinite replication capacity. The weakness of
the hES stem cell lines, which are currently approved for federal funding,
is that differentiation is difficult to control. These stem cell lines
also have the potential for tumor formation, cover only limited immunotypes,
and are contaminated with bovine and murine proteins/pathogens.
The strengths of
adult multipotent stem cells are abundance, more uniform differentiation,
restricted differentiation potential, and the potential for use in autologous
therapies that use the patient's own tissue. The weaknesses of adult stem
cells are limited replication potential and plasticity-the ability to
build tissue. Adult stem cells are readily available in adipose tissue,
because fat is plentiful and easy to collect. The resident stem cells
are more abundant in adipose tissue than in bone marrow, which are more
difficult and painful to harvest.
Sources of Stem
Cells and Stem Cell Therapies
stem cell sources are blood, bone marrow, adipose tissue, and dura mater.
Blood and blood components that are separated by a technique called apheresis
contain at least four types of stem cells. Multipotent stem cells are
important in bone marrow transplants, because they migrate to the recipient's
bone marrow and differentiate to produce all types of blood cells, fat,
cartilage, bone, muscle, adipose tissues, nerve cells, and glia-the supporting
tissue of the brain and spinal cord.
Umbilical cord blood
has some advantages over bone marrow and other blood. For example, cord
blood is almost pure stem cells, and because it is young it lacks cell
markers; it reproduces into mature, functioning blood cells faster and
more effectively than in bone marrow stem cells taken from a donor. Also,
because the T-cells at this young stage are not yet completely functional,
there is less risk of severe graft-versus-host disease.
On the other hand,
because of the presence of mature, fully functioning immune cells that
exist in pancreatic islet cells transplanted to treat Type I diabetes,
the risk of graft-versus-host disease is high. The treatment offers a
cure, but it requires lifelong treatment with immunosuppressants.
also uses adipose, muscle, blood vessels, and bone to mold new tissues,
with the lasting results attributable to the stem cells in the transplanted
tissue. Multilineage cells from human adipose, tissue have been shown
to differentiate in vitro to become cells that may form fat, cartilage,
muscle, and bone under the proper environmental conditions.
that depend primarily on stem cells include blood and blood product transfusions
and infusions, bone marrow transplants, pancreatic islet transplantation,
organ transplantation, reconstruction with autologous tissues, and fertility
and contraception treatments. Bone marrow stem cells are used to replace
diseased bone marrow in leukemias, aplastic anemia, and sickle cell anemia.
These stem cells can also be used to rescue damaged bone marrow after
radiation or chemotherapy in lymphomas, neuroblastomas, and breast cancers.
Virginia Stem Cell Related Activities
University of Virginia, embryonic stem cell research using mice is centered
on kidney development, smooth muscle differentiation, and bone regeneration.
Human embryonic stem cell research at UVA involves the study of smooth
muscle differentiation and bone regeneration and uses only NIH approved
cell lines. In 2004, 48 adult and 1 pediatric transplants were performed
at the University. Over the past 12 months, 8 pediatric bone marrow, cord
blood, and peripheral blood transplants were performed.
procedures involving knee joints, nerves, and the cranial bones have been
developed and are being advanced. Dr. Ogle showed slides of the regeneration
of the skull of a 7-year-old child who had received treatment with autologous
bone, adipose stem cells, and fibrin glue. He also showed slides of the
reconstruction of facial atrophy of a 17-year-old German child. The remarkable
results in both of these children are attributed to stem cell therapies.
Pancreatic islet cell transplantation is performed on individuals having
Type I diabetes.
Adult or multipotent
stem cells are used as model systems in research laboratories at the University
of Virginia in studies of myeloid leukemia, diabetes, breast cancer, blood
vessel formation, heart function, renal failure, and fracture healing.
Benefits to Virginians
from Stem Cell Research and Therapy
concluded his presentation by reviewing the potential benefits of stem
cell research and therapy:
- Improved quality
of health care.
- Reduction in the
cost of health care and long-term care.
- Increased productivity.
- Economic development
He also listed the
characteristics of a national immunotype library that would establish,
characterize, and distribute embryonic stem cells. A national immunotype
library would be created by a pending federal bill, HR 810.
UNIVERSITY SCHOOL OF MEDICINE PRESENTATION
Dr. Jerome F. Strauss,
Dean of the Virginia Commonwealth University School of Medicine and Executive
Vice President for Medical Affairs of the VCU Health System, came to VCU
from the University of Pennsylvania Medical Center where he also serves
as Director of the National Cooperative Center in Infertility Research.
Dr. Strauss's research interests include regulation of steroid hormone
biosynthesis, the genetics of polycystic ovary syndrome; trophoblast differentiation
and placental endocrine function, biology of fetal membranes; molecular
control of sperm motility; and embryonic stem cell differentiation. Dr.
Strauss's presentation focused on the role of regenerative medicine at
Virginia Commonwealth University.
University's strategic blueprint enables research in genetics, bioinformatics,
the neurosciences, microbiology and immunology, cellular and molecular
biology, and structural biology. VCU's mission is based on research goals
relating to maternal and child health, behavioral medicine, pathogens
and the environment, aging and metabolism, cancer, cardiopulmonary disease,
and especially, regenerative medicine. The rationale for emphasizing regenerative
medicine is to reduce unmet needs and health care costs and increase accessibility
to quality health care. Dr. Strauss explained that the aging of Virginia's
population and the concomitant burden of chronic disease, the expense
of more invasive therapies, and the complex health issues created by trauma,
war, natural disasters, and bioterrorism render regenerative medicine
an attractive alternative.
Dr. Strauss elaborated
on the appeal of embryonic stem cells, explaining that they are immortal,
can be cloned, are undifferentiated, and have great developmental potential.
He also discussed challenges to the development of embryonic stem cell
- Definitive proof
of embryonic stem cell capabilities has not yet been discovered.
- Purity remains
a problem in the approved cell lines because of contamination with bovine
and murine cells.
- Limited number
of available immunotypes.
- Apparent genetic
instability and risk of cancer.
- Difficulties in
production, as well as and the ethical issues.
- Ongoing controversy
concerning whether embryonic or adult stem cells are more efficient.
- Alternative proposals
for generating pluripotent cells.
- Appropriate development
of preclinical models.
- Whether intellectual
property is in the public or private domain.
Dr. Strauss mentioned
several alternatives to stem cell therapeutics, such as isolation of stem
cells from extraembryonic fetal tissues, activation of endogenous stem
cells, chemical or genetic initiation of nuclear reprogramming of adult
cells to be like the embryonic cell, and various biomaterials and devices.
at Virginia Commonwealth University
Medicine at VCU involves interaction between the transplant center, level
I trauma center, burn center, and Reanimation Engineering Shock Center
(VCURES). The goal of the regenerative medicine initiative is to advance
organ and cell transplantation and clinical application and research in
stem cells. Development of biomaterials and devices, as well as drugs
and biologicals is also key. In addition, VCURES, a multidisciplinary
collaboration among clinicians, basic scientists, and engineers, is working
on microvascular response to hemorrhagic shock, acute decompression illness,
and blood substitute development, which is particularly relevant to stem
University's Stem Cell Related Activities
time, VCU's stem cell related activities are focused on adult stem cells,
alternative strategies, the interface between engineering and biology,
and activation of endogenous stem cells. Over 200 bone marrow transplants
are performed each year. The bone marrow transplant center at VCU is a
recognized National Marrow Donor Program that performs both pediatric
and adult transplants and bone marrow harvests. The organ transplant program
includes liver, pancreas, kidney, pancreas-kidney transplants (for Type
I diabetics with end stage renal disease), islet cell transplantation,
heart, lung, and heart-lung transplants. VCU's Institute for Structural
Biology and Drug Discovery and the Institute for Oral and Craniofacial
Molecular Biology, among others, are housed at the Virginia BioTechnology
Dr. William J. Wasilenko
is the Associate Dean for Research and Adjunct Associate Professor in
the Department of Microbiology and Molecular Cell Biology at Eastern Virginia
Medical School (EVMS). Dr. Wasilenko directs the EVMS Biomedical Sciences
Ph.D. Program and is administrative director of the EVMS Biotechnology
Workforce Training Program. Dr. Wasilenko's research interests include
tumor and cell biology, signal transduction, and medical modeling and
Dr. Wasilenko began
his presentation by noting that EVMA was founded in 1973 and is a much
smaller institution than either the University of Virginia or Virginia
Commonwealth University. EVMS, however, is highly regarded as a cutting
edge institution in reproductive technology, and the medical school's
Jones Institute is well known throughout the world for its infertility
researchers at EVMS derived three embryonic stem cell lines from human
blastocysts created through in vitro fertilization using donor gametes.
Dr. Wasilenko clarified that no human embryonic stem cell research is
being conducted at this time, and that the researchers who conducted and
published the 2001 study are no longer at the medical school.
Current EVMS Stem
Cell Related Activities
Currently, EVMS has stem cell related activities in regenerative medicine
in diabetes. The Research Institute of the Strelitz Diabetes Institutes
at EVMS has conducted pioneering research with the pancreatic islet neogenesis
associated protein, commonly referred to as INGAP. In 1997, the Institutes
announced the discovery of the INGAP gene, as part of ongoing research
relating to genes and protein products that may cause pancreatic islet
cells to regenerate and produce insulin. Subsequent work has been focused
on the purifying and engineering of the gene. Phase II Clinical Trials
are in progress on the results of some of the Institute's work. Other
stem cell related activities relate to the treatment of various cancers,
infectious diseases, and reproductive and infertility disorders. EVMS
also collects cord blood, if the parents so wish.
WORK PLAN &
The Joint Subcommittee
discussed plans for its final meeting, which will be held on November
15, 2005, and will include an additional presentation on Virginia stem
cell activities, a public hearing, and a work session for determining
findings. Pictures from the September meeting and materials and audio-streaming
from the previous meeting may be accessed on the study website.
The Hon. R.G. Marshall
DLS Staff Attorney