C-kit+AT₂R⁺ Bone Marrow Mononuclear Cell Subset Is A Superior Subset For Cardiac Protection After Myocardial Infarction

Although the bone marrow mononuclear cell?BMMNC?is known as an ideal cell type for cell-based therapy for myocardial infarction?MI?treatment,the effective subpopulation still remains unknown.Therefore,identifying the optimal subset of BMMNCs suited for cardiac regeneration is a key step toward improving clinical outcomes.In this study,we evaluated if bone marrow-derived c-kit+AT₂R+BMMNCs may play a protective role in myocardial infarction-induced cardiac remodeling.We observed that MI led to i.)a significant increase of the c-kit+AT₂R+BMMNC subpopulation in mice and ii.)a modest increase of AT₂R+BMMNCs in humans.Fluorescence-activated cell sorting?FACS?was performed to harvest c-kit+AT₂R+and c-kit+AT₂R-BMMNC subpopulations from mice after MI.Then,we co-cultured cardiac H9C2cells with c-kit+AT₂R+,c-kit+AT₂R-and unfractionated BMMNCs,finally,we found that the c-kit+AT₂R+subset is superior to the c-kit+AT₂R-subset in improving cardiomyocyte protection in vitro.Of note,c-kit+AT₂R+BMMNCs showed a more robust migration capacity than c-kit+AT₂R-and unfractionated BMMNCs in vitro and in vivo.Additionally,compared to c-kit+AT₂R-and unfractionated BMMNCs,intravenous transplantation of c-kit+AT₂R+BMMNC resulted in smaller infarct size and lower levels of inflammatory reactions in heart tissue,leading to a higher global heart function improvement.In conclusion,the c-kit+AT₂R+BMMNC subpopulation exerts a protective effect against MI and may show therapeutic possibilities with regard to the treatment of ischemic heart disease.