The Enormous Potential Value of Stem Cell Research
cell research is a step to be taken toward the improvement of transplantation
therapy and toward lengthening a person's life.We will postpone discussion of life-extension, noting here the relevance to
transplantation medicine. Specifically, rejuvenation through transplantation of
tissue grown in a laboratory from stem cells would be of enormous value for cardiomyocytes to renew heart muscle to
prevent congestive heart failure; replacement of hematopoietic stem cells for producing healthy blood in bone
marrow to resist infection by the human immunodeficitent virus and to treat
AIDS and possibly sickle cell anemia; cultivating endothelial cells to reline blood vessels as treatment for
atherosclerosis, angina, and stroke due to arterial insufficiency; rejuvenating
islet cells in the pancreas to
produce natural insulin to fight diabetes; renewal of neurons in the brain to treat Parkinson's
disease and victims of stroke; fibroblast
and keratinocyte cells to heal skin in the treatment of burns; and chondrocytes or cartilage cells to treat
osteoarthritis or rheumatoid arthritis.
trick will be to discover just what turns which genes on and off. Once
scientists have learned how to trigger gene expression, they can apply it to
pluripotent stem cells and direct the growth of selected bodily tissue.
Particular organs could be grown in culture. Heart tissue or entire organs such
as the pancreas or liver could be grown in the laboratory. These would be
healthy rejuvenating organs ready for transplantation.
order to transplant the laboratory grown organs, however, we need to override
our immune system in order to avoid organ rejection. Two scenarios lie before
us. One would be to create a 'universal donor' cell that would be compatible
with any organ recipient. The task here would be to disrupt or alter the genes
within the cell responsible for the proteins on the cell's outer surface that
label them as foreign to the recipient's immune system. This approach would be
difficult. It would involve disrupting genes within the same DNA in which we
are trying to express certain other genes. Exposing such cells to harsh
conditions with rounds of different drugs may damage more than just the
targeted surface proteins.
preferable second scenario would be to make cells that are genetically
compatible (histocompatible) with the organ recipient--that is, to make cells
with an identical genotype. If the organ genotype matches that of the
recipient, no immune system rejection will take place.
cloning--that is, somatic cell nuclear transfer. We can imagine the following
scenario for customizing organ growth and transplantation. We could begin with
an enucleated human oocyte--that is, we could begin with an egg with the DNA
nucleus removed. Via somatic nuclear transplantation--cloning--we could insert
the DNA nucleus of the future transplant recipient. We could then turn on
selected genes--that is, we could cause the stem cell to differentiate into
cardiomyocytes to produce heart tissue. The heart tissue could be grown ex vivo, outside the body, and then
through surgery placed within the recipient. Because the implanted heart tissue
has the same genetic code as the recipient, no rejection would occur. This is
in part the Dolly scenario. It differs in part because it grows only organ
tissue and not an entire fetus.
variant on the second scenario that distinguishes it from Dolly would be one
that eliminates the use of the oocyte. Instead of an oocyte, the recipient's
DNA nucleus might be placed within a non-egg cell. The goal would be to
accomplish laboratory organ growth in a stem cell that is not an egg. To
accomplish this, we need further research on cytoplasm's role in gene
is there in the cytoplasm that programs the DNA? Could we discover this? If so,
we could begin not with an oocyte but rather with an hES cell. We could
enucleate a non-egg stem cell and insert the specific DNA nucleus, then
reprogram the cytoplasm to cause the desired differentiation.
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| Contributed by: Dr. Ted Peters