Abstract

Background: Cardiac cell-based therapy (CCT) has emerged as a promising therapeutic strategy. There are few data comparing the fate of different stem cell (SC) populations delivered by the intracoronary injection (ICI). Aim: Document the in vivo myocardial distribution of SC delivered by ICI following recent myocardial infarction. Methods: In a myocardial infarction swine model, near-infrared (NIR) fluorescence was used to provide high sensitivity in vivo tracking of SC in the immediate phase (< 60 minutes) after ICI of 2x107 cells. After labeling with the NIR fluorophore, IR-786, the NIR signal intensities and myocardial distribution patterns of mesenchymal (MSC), bone marrow-(BMMNC) and peripheral blood-mononuclear (PBMNC) cells were compared using an open-chested fluorescence imaging system. Results: The SC populations of interest were successfully loaded with IR-786. While all SC populations readily distributed along the vascular territory of the infarct-related artery immediately after injection, there was a mean SI intensity drop of 29.8% and 14.1% for PBMNC and BMNC (p<0.05), respectively, which correlated with poor cell retention. No significant SI change was found in MSC-injected swine, which was associated with less cell loss after delivery. There was also evidence of MSC-related vessel plugging in some swine (Figure ). Conclusion: Our in vivo findings suggest that immediately after injection (during the first 60min ICI), there is already evidence of poor SC retention and distribution vary depending on cell population, potentially impacting clinical efficacy and safety of CCT.

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