Paracrine Action of Mesenchymal Stem Cells Revealed by Single Cell Gene Profiling in Infarcted XXXX Hearts.

@entity19 @entity519 @entity1188
BACKGROUND: Mesenchymal stem cells (MSCs) have been recently demonstrated as a promising stem cell type to rescue damaged myocardium after acute @entity1188 . One of the most important mechanisms underlying their therapeutic effects is the secretion of paracrine factors. However, the expression profile of paracrine factors of MSCs in @entity1188 hearts, especially at single cell level, is poorly defined. METHODS AND RESULTS: We aimed to depict the transcriptional profile of paracrine factors secreted by MSCs in vivo, with particular interest in the comparison between normal and @entity1188 hearts. Bone marrow mesenchymal stem cells were isolated and injected into @entity19 hearts immediately after @entity1188 surgery. Bioluminescence imaging (BLI) indicated a proportion of cells still alive even up to 10 days post surgery. Paralleled with survived cells, cardiac function was significantly improved after MSC injection compared to that in PBS-injected @entity19 , indicated by MRI and histology. Despite increased number of vessels in MSC-injected hearts, endothelial cells and cardiomyocytes transdifferentiation were not observed in @entity1188 hearts 5 days after @entity1188 . Furthermore, laser capture microdissection (LCM) followed by high through-put real time PCR was employed in our study, uncovering that the injected MSCs, compared to local cardiomyocytes, displayed elevated levels of secreted factors. To further investigate the regulation of those factors, we performed single cell analysis to dissect the gene expression profile of MSCs at single cell level in @entity1188 and normal hearts, respectively. Consistent with the in vivo observation, a similar regulation pattern of those factors was detected in cultured MSCs under @entity519 . CONCLUSIONS: Our study, for the first time, elucidated gene expression profiles, as well as regulation of paracrine factors, of MSCs at single cell level in vivo, indicating that paracrine factors from MSCs account for the improvement of cardiac function after @entity1188 .
