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 MI treatment, the effective subpopulation still remains unknown. Our study aimed at identifying the optimal subset of BMMNCs suited for cardiac regeneration. In this study, 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. c-kit+AT2R+ and c-kit+AT2R− BMMNC subpopulations were obtained from mice after MI. Then, we cocultured cardiac H9C2 cells 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, our results indicate that the c-kit+AT2R+ BMMNC subpopulation exerts a protective effect against MI and shows promising therapeutic possibilities with regard to the treatment of ischemic heart disease.

尽管骨髓单个核细胞（BMMNC）被认为是用于心肌梗死（MI）治疗的细胞疗法的理想细胞类型，但其有效的亚群仍然未知。我们的研究旨在确定适合心脏再生的BMMNC的最佳亚群。在本研究中，我们观察到心肌梗死导致（i）小鼠中c - kit⁺AT2R⁺ BMMNC亚群显著增加，以及（ii）人类中AT2R⁺ BMMNC适度增加。从心肌梗死后的小鼠中获得了c - kit⁺AT2R⁺和c - kit⁺AT2R⁻ BMMNC亚群。然后，我们将心脏H9C2细胞与c - kit⁺AT2R⁺、c - kit⁺AT2R⁻以及未分选的BMMNCs共培养；最后，我们发现在体外改善心肌细胞保护方面，c - kit⁺AT2R⁺亚群优于c - kit⁺AT2R⁻亚群。值得注意的是，在体外和体内，c - kit⁺AT2R⁺ BMMNCs比c - kit⁺AT2R⁻和未分选的BMMNCs显示出更强的迁移能力。此外，与c - kit⁺AT2R⁻和未分选的BMMNCs相比，静脉移植c - kit⁺AT2R⁺ BMMNC导致心脏组织中的梗死面积更小，炎症反应水平更低，从而使整体心脏功能得到更高的改善。总之，我们的结果表明，c - kit⁺AT2R⁺ BMMNC亚群对心肌梗死具有保护作用，并在缺血性心脏病的治疗方面显示出有前景的治疗可能性。