Down-Regulated Exosomal MicroRNA-221 – 3p Derived From Senescent Mesenchymal Stem Cells Impairs Heart Repair

• Published in: Frontiers in cell and developmental biology Vol. 8; p. 263
• Main Authors: Sun, Ling, Zhu, Wenwu, Zhao, Pengcheng, Zhang, Jian, Lu, Yao, Zhu, Yeqian, Zhao, Wei, Liu, Yaowu, Chen, Qiushi, Zhang, Fengxiang
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 05.05.2020
• Subjects: acute myocardial infarction; Cell and Developmental Biology; exosomes; mesenchymal stem cells; microRNA-221-3p; senescence; senescence; exosomes; mesenchymal stem cells; microRNA-221-3p; acute myocardial infarction
• ISSN: 2296-634X; 2296-634X
• DOI: 10.3389/fcell.2020.00263

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 ; and improving cardiac structure and function 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.