Bone marrow stem cell (BMSC) therapy holds promise for patients suffering from heart disease. Althoughclinical trials have begun, basic understanding of BMSC biology remains limited. This proposal investigatesBMSC therapy using murine models of ischemic heart disease.
In Aim 1, BMSCs constitutively expressing molecular imaging reporter genes will be transplanted intonormal myocardium to assess survival by noninvasive imaging.
In Aim 2, we will define the therapeuticefficacy of these cells by transplantion into acute and chronic models of ischemic heart disease, followed bymulti-modality assesment of cardiac function.
In Aim 3, we will investigate the mechanims by which BMSCsengraft, differentiate, and respond to host myocardium by gene expression profiling of BMSCstransplantedinto acute and chronic ischemic cardiac milieus. The overall significance of this project is two-fold: (1) to define the survival kinetics of BMSCs in vivo and(2) to understand the mechanisms by which BMSC therapy can induce functional improvement.
|Sheikh, Ahmad Y; Huber, Bruno C; Narsinh, Kazim H et al. (2012) In vivo functional and transcriptional profiling of bone marrow stem cells after transplantation into ischemic myocardium. Arterioscler Thromb Vasc Biol 32:92-102|
|Sheikh, Ahmad Y; van der Bogt, Koen E A; Doyle, Timothy C et al. (2010) Micro-CT for characterization of murine CV disease models. JACC Cardiovasc Imaging 3:783-5|
|Sheikh, Ahmad Y; Chun, Hyung J; Glassford, Alexander J et al. (2008) In vivo genetic profiling and cellular localization of apelin reveals a hypoxia-sensitive, endothelial-centered pathway activated in ischemic heart failure. Am J Physiol Heart Circ Physiol 294:H88-98|