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Rachel J. Nielsen '04
Faculty Mentor: Dr. Mark D. Kirk, Biological Sciences Funded by National Science
Foundation - REU (Life Sciences)
Title: Double labeling for neural markers of neuralized mouse embryonic stem cells
and effects of immunosuppression on stem cell integration into the injured murine retina
Abstract: Embryonic stem (ES) cells provide promising opportunities for the treatment
of degenerative diseases because these cells have the ability to differentiate into any
cell type and they have the potential to divide indefinitely. We are looking at a certain
group of neurodegenerative diseases called the neuronal ceroid-lipofuscinoses
(NCLs) also known as Batten Disease. In humans, these disorders are characterized
by degeneration in the retina and central nervous system (CNS) that leads to blindness,
seizures, cognitive decline and premature death. We propose that stem cells can
replace the cells lost in the retina and CNS due to the disease process underlying
NCLs. Alternatively, stem cells maybe used to deliver therapeutic agents that will
prevent neurodegeneration due to the NCLs.
One of the drawbacks of ES cell therapy is the possibility that the host's immune
system might attack and kill the transplanted ES cells rendering them useless. We
examined if immunosuppression is necessary for neuralized mouse ES cells to
integrate and survive in the retinas of mice that exhibit rapid retinal degeneration.
Since the mammalian eye is to a great extent immune privileged, we expect to see
that there is no need to immunosuppress the subjects for this type of therapy. We
chose CBA/J mice, a strain of mice with rapid retinal degeneration, as our model
organism. We transplanted neuralized mouse ES cells into the eyes of 5 CBA/J mice.
Three of these mice were immunosuppressed with daily oral doses of cyclosporin
(10mg/kg), and left 2 CBA/J mice with functioning immune systems and transplants of
neuralized ES cells as controls. We determined that mouse ES cells survived and
integrated into the eyes of both groups of mice.
We also performed double-labeling experiments to test whether individual neuralized
mouse ES cells grown in culture can express more than one type of neural marker.
We did not find any stem cells that expressed both astrocyte and neuronal markers.
The website were you can get more information about the research going on at the University of Missouri - Columbia is as follows -- http://www.lsurop.missouri.edu.
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