Year: 2012
Type: article
Abstract: Cardiovascular disease is the leading causeof death in the industrialized world and its prevalence is
increasing worldwide. Regenerative medicine represents a new
medical frontier for the treatment of heart failure. This
therapeutic approach has mainly focused on the delivery of
exogenous stem cells. While clinical trials have shown no major
safety concerns, the outcomes associated with the use of exogenous
stem cells have shown some degree of efficacy in selected cases. In
addition to exogenous stem cells, endogenous populations of stem
cells exist and can be activated to promote tissue healing.
However, the exact role of endogenous stem cells in cardiac
regeneration is far from clear. In Chapter
Three, we examined the response of endogenous stem cells to
trans-aortic constriction (TAC) in a mouse model. Our results
demonstrated an early, orchestrated systemic response of cardiac
stem cells (CSC), endothelial progenitor cells (EPC), and SSEA1+
stem cells following TAC. The most significant response found was
in the splenic and bone marrow EPC and SSEA1+ populations. These
cells showed early mobilization and accumulation in the heart,
prior to any proliferative response. Peak stem cell content in the
myocardium occurred at 7 days post-TAC. These data identify stem
cell sources and populations respondent to TAC.
Chapter Four focuses on bone marrow SSEA1+
cells. Through chimeric bone marrow studies, we found that SSEA1+
cells can differentiate into other cells types, including
hematopoietic stem cells, EPC, and endothelial cells. We also
determined that bone marrow SSEA1+ cell support is essential in
maintaining cardiac homeostasis after TAC. Depletion of bone marrow
SSEA1+ cells quickened cardiac dysfunction and increased vessel
rarefaction after TAC. These results have begun to define the fate
and function of bone marrow SSEA1+ cells. The data presented in
this dissertation demonstrate a strong support of the myocardium by
peripheral stem cells. The next generation of stem cell therapies
may focus on manipulating the endogenous peripheral stem cells as
well as the local CSC.
Author: Amanda Finan-Marchi
Institution: Case Western Reserve University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2260411261