Cardiac Derived CD51-Positive Mesenchymal Stem Cells Enhance the Repair of Infarcted Heart in Mice Through SCF-Mediated Angiogenesis

Background: A number of tissues contained resident mesenchymal stromal/stem cells (MSCs), and these ideal MSCs candidates were crucial regulators for tissue hemostasis or repair. However, the marker to identify cardiac resident MSCs remains poorly understood. This study was aimed to determine CD51 as a promising marker of MSCs in the hearts, and explore their therapeutic potential for acute myocardial infarction (AMI) disease. Methods: Cardiac derived CD51+CD31-CD45-Ter119- cells (named CD51+MSCs) were isolated from C57BL/6 mice of 7-day-old by flow cytometry. The characteristics of CD51+MSCs were identified by proliferation, multi-differentiation assay, and expression of MSCs markers. C57BL/6 mice of 8-week-old were utilized for AMI model via permanently ligating the left anterior descending coronary artery. The therapeutic efficacy of CD51+MSCs were estimated by echocardiography and Masson's trichrome staining. To determine the underlying mechanism, candidate lentivirus was utilized to silence gene expression in CD51+MSCs. Findings: In this study, CD51 positive cells were present in the hearts of mice, and diffusely distributed in the endocardium, epicardium and myocardium. Interestingly, the cultured cardiac CD51+MSCs expressed MSCs-related markers, possessed self-renewal potential and multi-lineage differentiation capacity in vitro. Furthermore, CD51+ MSCs-based therapy contributed to improvement of cardiac function and attenuation of fibrosis by enhancing angiogenesis. Moreover, stem cell factor (SCF) secreted by CD51+ MSCs played a role to angiogenesis function of endothelial cells both in vivo and in vitro. Interpretation: Collectively, our results identified CD51 as a novel marker of cardiac resident MSCs for therapy of AMI, and revealed SCF-mediated angiogenesis mechanism induced by CD51+ MSCs treatment. Funding Statement: This work was supported by National Key Research and Development Program of China (2017YFA0103802), the National Natural Science Foundation of China (grant no. 31972894, 81770290, 81370214, 81425016, 81700484), the China Postdoctoral Science Foundation (2018M633251), Natural Science Foundation of Guangdong Province (S2013010016392, 2017A030310234), Science and Technology Planning Project of Guangdong Province ((2016B030229006, 2014B020228001, 2014B020226002, 2014A020211007), the Key Scientific and Technological Program of Guangzhou City (201604020158), the Fundamental Research Funds for the Central Universities (14ykpy01, 18ykpy39). Declaration of Interests: There are no relationships with industry. All authors declare no financial conflict of interest. Ethics Approval Statement: All animal protocols were reviewed and approved by the Sun Yat-Sen University Institutional Animal Care and Use Committee.