miR‐155‐5p inhibition rejuvenates aged mesenchymal stem cells and enhances cardioprotection following infarction

• DOI: 10.1111/acel.13128
• Publication Date: 2020-03-20T18:37:38Z
• Authors: Yimei Hong; Haiwei He; Guojun Jiang; Hao Zhang; Wuyuan Tao; Yue Ding; Dongsheng Yuan; Jing Liu; Huimin Fan; Fang Lin; Xiaoting Liang; Xin Li; Yuelin Zhang
• Keywords: Senescence; Cardioprotection

Abstract Aging impairs the functions of human mesenchymal stem cells (MSCs), thereby severely reducing their beneficial effects on myocardial infarction (MI). MicroRNAs (miRNAs) play crucial roles in regulating senescence MSCs; however, underlying mechanisms remain unclear. Here, we investigated significance miR‐155‐5p MSC and whether inhibition could rejuvenate aged MSCs (AMSCs) to enhance therapeutic efficacy for MI. Young (YMSCs) AMSCs were isolated from young donors, respectively. The cellular was evaluated by senescence‐associated β‐galactosidase (SA‐β‐gal) staining. Compared with YMSCs, exhibited increased as evidenced SA‐β‐gal activity decreased proliferative capacity paracrine effects. expression much higher both serum donors than donors. Upregulation YMSCs led senescence, whereas downregulation AMSC senescence. Mechanistically, inhibited mitochondrial fission fusion via AMPK signaling pathway, resulting repressing Cab39. These partially reversed treatment activator or mitofusin2‐specific siRNA (Mfn2‐siRNA). By enhancing angiogenesis promoting cell survival, transplantation anti‐miR‐155‐5p‐AMSCs improved cardiac function an mouse model MI compared AMSCs. In summary, our study shows that mediates Cab39/AMPK pathway is a novel target cardioprotective