AUTHOR=Sun Ling , Zhu Wenwu , Zhao Pengcheng , Zhang Jian , Lu Yao , Zhu Yeqian , Zhao Wei , Liu Yaowu , Chen Qiushi , Zhang Fengxiang TITLE=Down-Regulated Exosomal MicroRNA-221 – 3p Derived From Senescent Mesenchymal Stem Cells Impairs Heart Repair JOURNAL=Frontiers in Cell and Developmental Biology VOLUME=8 YEAR=2020 URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2020.00263 DOI=10.3389/fcell.2020.00263 ISSN=2296-634X ABSTRACT=

The composition and biological activity of donor cells is largely determined by the exosomes they secrete. In this study, we isolated exosomes from young (Young-Exo) and aged (Age-Exo) mesenchymal stem cells (MSCs) and compared their regeneration activity. Young Exo MSCs were more efficient than Aged-Exo at promoting the formation of endothelial tube, reducing fibrosis, and inhibiting apoptosis of cardiomyocytes in vitro; and improving cardiac structure and function in vivo in the hearts of rats following myocardial infarction (MI). MicroRNA sequencing and polymerase chain reaction (PCR) analysis revealed that miR-221-3p was significantly down-regulated in Aged-Exo. The aged MSCs were rejuvenated and their reparative cardiac ability restored when miR-221-3p was overexpressed in Aged-Exo. The protective effect was lost when miR-221-3p expression was knocked down in Young-Exo. These effects of miR-221-3p were achieved through enhancing Akt kinase activity by inhibiting phosphatase and tensin homolog (PTEN). In conclusion, exosomal miR-221-3p secreted from Aged MSCs attenuated the function of angiogenesis and promoted survival of cardiomyocytes. Up-regulation of miR-221-3p in aged MSCs improved their ability of angiogenesis, migration and proliferation, and suppressed apoptosis via the PTEN/Akt pathway.