Role of Oxidative Stress in Stem Cell Differentiation and Survival

Project: Research project

Project Details


ABSTRACT: Stem cell transplantation offers much promise as a potential treatment for myocardial salvation
at the end stages of coronary artery disease (CAD), and much interest has been placed in the differentiation
capacity of different population of stem cells. However, little is known about the regulatory mechanisms of
stem ceil differentiation In vivo, and under hostile conditions, like myocardial infarction. Myocardial infarction
leads to changes In the local microenvironment and Increases oxidative stress, which can regulate cellular
differentiation and survival. The long term goal of our program is to study the biology of stem cells after
transplantation to the heart. Our primary hypothesis In this proposal is that changes in oxidant status play a
role in stem cell differentiation and sun/ival in the mycoardium. To test that hypothesis we have the following
specific aims: in Specific Aim 1 we will differentiate bone marrow stromal cells Into cells with myocyte
characteristics, both in cell culture and in living subjects, and we will use molecular techniques to track this
differentiation non-invasively, something that could be done until recently. For that purpose we will use
reporter imaging technology and optical imaging, in Specific Aim 2, we will examine if increased oxidative
stress is involved In stem ceil differentialton and sun/ival. For that, will be induced in cell culture and in living
subjects (after myocardial infarction), after which stem cell differentiation and survival will be tracked using
molecular imaging techniques (optical imaging). In addition, we will study pathways related to oxidative
stress (i.e. nitric oxide), and examine their role in stem cell differentiation. Lastly in Specific Aim 3, we will
learn from Aims 1 and 2 and "genetically engineer" stem cells so they are better prepared to differentiate and
survive in hostile condition, like the one found in states of myocardial ischemia and infarction.
The studies proposed in this grant will provide invaluable information on the role that the microenvironment
plays in stem cell differentiation and survival and can lead to novel and improved therapeutic strategies.
Stem cell therapy provides a great opportunity to re-constitute a damaged heart, but we first need to
elucidate the mechanisms that regulate stem cell differentiation and sun/ival. In this study we propose that
specific biological pathways (i.e. oxidant status) can be involved in such response. Understanding these
mechanisms that regulate stem cell survival will lead to better and improved therapies.
StatusNot started


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