? There has been growing evidence that bone marrow derived stem cells injected into areas of damaged myocardium prevent deleterious remodeling of the post-myocardial infarcted heart. However, the survival and function of these bone marrow derived stem cells (BMC) once injected are not known. Therefore, the main goals of this proposal are to use newly developed molecular probes from our laboratory to track BMC and to understand the biology of integration and the cellular fate of BMC in a large animal model of myocardial infarction and remodeling. These novel molecular probes generate contrast simultaneously for both magnetic resonance imaging (MRI) and near-infrared (NIR) fluorescent optical imaging. MRI permits BMC to be identified in the normal and diseased hearts of large animals over time, non-invasively, and without sacrifice of the animal. NIR fluorescent optical imaging provides high sensitivity, and in some cases single cell sensitivity, which can be used for intraoperative physiological studies and for histological correlation with other markers of cardiomyocyte function.
In Specific Aim 1 we will test and validate novel MRI/optical dual-modality contrast agents already developed by our laboratories in isolated bone marrow cells from pigs.
In Specific Aim 2 we will use an established non-invasive catheter technique or use a surgical open-chested technique under NIRF guidance to deliver autologous stem cells in normal swine left ventricles.
In Specific Aim 3 we will use an established non-invasive catheter technique or use a surgical open-chested technique under NIRF guidance to deliver autologous stem cells in a swine model of myocardial infarction. Our ability to distinguish and retrieve implanted cells will also enable us to directly assess the molecular and functional status of BMC following cardiomyogenic differentiation. The knowledge gained from this proposal will contribute to the usage of newly developed dual probes with the capability of being visible at both near-infrared and also by magnetic resonance imaging and also will enhance our understanding of the cellular fate of implanted BMCs and their cellular function following cardiomyogenic-differentiation. This will ultimately advance the field of stem cell biology and cell-based therapies for the treatment of cardiovascular diseases. (End of Abstract) ? ? ?
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