Abstract 856: Genomic Profiling of Bone Marrow Cells Transplanted Into the Heart
Background: Despite ongoing clinical trials, survival and function of transplanted bone marrow stem cells (BMSC) remains unknown.
Methods: BMSC were harvested from transgenic mice expressing firefly luciferase and green fluorescent protein reporter genes. 5×106 cells were injected into the left ventricle of syngeneic mice following 45 min LAD ischemia-reperfusion (IR, n=8) or sham procedure (n=8). In a separate cohort of animals (n=4 IR, 4 sham), BMSC were isolated from hearts 4 days post-injection and RNA hybridized to mouse whole genome arrays.
Results: Bioluminescence signals correlated linearly with BM cell numbers (r2=0.93) in vitro. FACS analysis revealed .07% of the isolate to be hematopoeitic stem cells. In both groups, cell signals peaked at day 4 and decreased significantly by 3 weeks. Echo showed a trend towards ventricular improvement with BMCS at week 6 (compared to saline injection alone). Microarray analysis revealed cells transplanted into ischemic myocardium had ~1500 upregulated and ~400 downregulated genes compared to cells in normal myocardium (FDR 5, p<0.05). Cluster analysis showed several of the upregulated genes were related to transcriptional activation and cell cycle. Down regulated genes included cell commitment, cell differentiation, and pattern specification.
Conclusions: This study integrates imaging and genomics to understand the fate of transplanted BMSC. In vivo imaging suggests lack of long-term engraftment while transcriptional profiling reveals a down regulation of transdifferentiation pathways, supporting earlier observations that transplanted BMSCs do not adopt adult myocardial fates.