Effect of estrogen on apoptotic regulatory mechanisms in mesenchymal stem cell maintenance
Author(s)
Advisor
Akçalı, K. CanDate
2006Publisher
Bilkent University
Language
English
Type
ThesisItem Usage Stats
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Abstract
Mesenchymal Stem Cells (MSCs) can both self-renew and differentiate into fat,
bone, cartilage, and muscle. They have a high therapeutic value due to their
differentiation potential and nonimmunogenic characteristics, however their rareness
and duration of their culture are the main handicaps in their application in cell-based
therapies. Therefore, our aim was to explore the possible mechanisms that are
involved in MSC maintenance and proliferation by using rat MSCs as a model. We
studied the effect of estrogen on MSCs due to its role in growth regulation,
differentiation, and cellular proliferation. In MSCs isolated from both normal and
ovariectomized animals, the number and the CFU activity were increased when
cultured with estrogen. To reveal the mechanism of the action of estrogen on MSC
maintenance, we investigated the apoptotic pathway since estrogen has been shown
to have a detrimental effect on apoptosis in other systems. The number of apoptotic
cells decreased when MSCs were cultured in the presence of estrogen. To elucidate
the molecular mechanism of estrogen’s effect on MSC apoptosis, we examined the
expression of the bcl-2 family of genes. The expression of anti- apoptotic Bcl-2 and
Bcl-xL proteins increased in the presence of estrogen, whereas the expression of proapoptotic
Bak decreased. Our results clearly show that estrogen increases the number
of the functional MSCs by differentially regulating the expression of the bcl-2 family
of genes and inhibiting apoptosis. Therefore estrogen treatment of MSCs may offer a
potential to increase the number of MSC for treatments.