Stem Cells and Aging
AGHE Annual Meeting
San Jose, California
February 22-25, 2001
Professor of Biology
Quinnipiac University
Hamden, Ct 06518
Tel. (203) 582-8676
Fax (203) 582-8706
E-mail:
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Introduction
Recent Advances in Stem Cell research
Embryonic Stem Cell (ESC) versus Adult Stem Cell
INTRODUCTION
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Until recently, scientists thought that cell’s fate is sealed and that after
embryonic development most cells were unable to divide.
Recently, however, new knowledge of stem cell biology has significantly
changed our views in this matter. Stem
cell technology is currently being developed
and in some cases implemented to generate new tissues to replace
diseased or aged tissue. Many
clinical sites have experimented with neuronal stem cell transplantation to
determine whether functional recovery can occur with central nervous system
(CNS) injury as well as neurodegenerative disorders such as Parkinson’s
Disease. In animal studies, the
results have been encouraging. For
example, transplantation of embryonic stem cells into injured spinal cord has
promoted functional recovery in the rat.
Furthermore, recent experimental results point to adult human tissues
as possible sources of stem cells. For
example, it is now well established that the adult human brain contains
pluripotent natural stem cells capable of differentiating into various cell
types and may, in the future, provide therapeutic avenues for variety of
diseases and aging changes such as Alzheimer’s disease.
RECENT ADVANCES IN STEM
CELL RESEARCH
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In August, 2000 Federal funding
for embryonic stem cell research was approved
with strict guidelines. Some of
the guidelines include:
Stem cells must come from human embryos that were surplus from fertility
clinic.
The embryos must have been frozen and the donors must be aware of the possible
use for medical research.
No financial incentives to create embryos for research.
Human embryonic stem cells were discovered in 1998 to successfully grow in
cell culture (James Thomson, University of Wisconsin and John Gearhart, John
Hopkins).
Stem cells are not embryos and cannot themselves develop into embryos.
However, they can be coaxed to differentiate into any type of cell,
hence open up the possibilities to treat variety of human ills, from diabetes
to Alzheimer’s. Politically,
they have been a tough sell since they are
derived from embryos and fetuses.
Margaret Goodell’s recent discovery suggest that stem cells derived from
adults
(mouse muscle biopsies) can perform many of the embryonic stem cells’
functions without the obvious ethical controversies.
Goodell’s work has led other investigators to show that adult bone marrow
stem cells can be converted into nerve cells; blood forming cells can be
converted into muscle cells; and neural stem cells, derived usually in a layer
of tissue that surrounds the ventricles (subventricular zone and the dendrate
gyrus of the hippocampus), can be coaxed into liver cells (Helen Blau,
Stamford).
Stem cells migrate widely if added to young brain but are fairly dormant in
healthy adult brain. However,
stem cells appear to somehow sense damage and, in adults, injuries prompt stem
cell migration to injured areas.
In monkeys with demyelinated lesions, stem cells are converted into glial
cells (oligodendrocytes) which form new myelin (Jeffrey Kocsis, Yale
University) In mice infected with
virus that causes same type of neural damage as amyotropic lateral sclerosis (ALS)
in humans, the virus kills neurons at the base of the spinal cord leading to
paralysis. When mouse stem cells
have been injected in the cerebrospinal fluid, cells migrate from top of
spinal cord to the base and cling to injured areas.
Eight weeks after receiving stem cells, half of the animals could move
their limbs somewhat (Jeffrey
Rothsteine, John Hopkins).
Amyloid protein injected in one side of the rats’ brain accumulate into
plaques characteristic of Alzheimer’s disease (control animals receive
benign protein injection). Stem
cell injected into the ventricles of the opposite side of the brain migrate
across the hemisphere and find their way into the amyloid deposits but ignore
the control protein (Barbara Tate, Children’s Hospital, Boston,
Massachusetts).
Karen Aboody’s (Children’s Hospital, Boston, Massachusetts) work has shown
that stem cells may be able to “chase down” brain tumor cells.
What currently is not well understood is:
What are these stem cells doing ?
Are they replacing dead cells? Improve
neuronal connections ? Perform
some other function ?
EMBRYONIC STEM CELL
(ESC) VERSUS ADULT STEM CELL
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Embryonic Stem Cell |
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In rodents, restores certain missing nerve functions |
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Less ability to differentiate than ESC except the
bone marrow stem cells which have the ability to differentiate into most
any type of a cell. |
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ES cells spontaneously differentiate into all kinds
of tissue. When injected
under the skin they grow into teratomas (tumor consisting of numerous
cell types from gut to skin). Before
applying these cells in human diseases, researchers must |
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Bone Marrow cells are very rare (1 out of 10 billion). More numerous in children. |
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Infinite in their ability to divide (some mouse ES
cell lines have been around for over 10 years).
Human stem cells grow more slowly, divide less often in culture
and once transplanted into rodents, they are less predictable.
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They lose their ability to divide and differentiate after a time in culture. This short time span may make it unsuitable for some medical application. |
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Has been tested in the treatment of Parkinson’s
disease. When grafted into
brains of Parkinson’s patients it has, in many cases, dramatically
relieved the patients symptoms (up to 50% reduction in symptoms and the
effects appear to last).
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It takes 6 fetus to provide enough materials to treat one Parkinson’s patient in part because 90 to 95% of neurons die shortly after grafting. |
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Copyright 2000 Ken
Kaloustian, Ph.D.