Exosomes derived from human umbilical cord mesenchymal stem cells repair injured endometrial epithelial cells.

Abstract

To investigate whether exosomes derived from human umbilical cord mesenchymal stem cells (hucMSC-derived exosomes) can repair injured endometrial epithelial cells (EECs). HucMSC-derived exosomes and mouse primary EECs were isolated and purified. EECs were exposed to oxygen and glucose deprivation for 2h followed by reoxygenation to mimic injury. After oxygen and glucose deprivation/reoxygenation (OGD/R), hucMSC-derived exosomes were added to the EEC culture medium. After 24h of co-treatment, cell viability and cell death were tested by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay and lactate dehydrogenase (LDH) assay, respectively. The expression of proinflammatory cytokines was tested by real-time PCR, enzyme-linked immunosorbent assay (ELISA), and Western blot to investigate the potential mechanism. Compared with the control group, 5, 10, and 15μg/mL of hucMSC-derived exosomes significantly attenuated cell viability decrease and inhibited LDH release of injured EECs, but 1μg/mL of hucMSC-derived exosomes had no effect on either cell viability or LDH release. Real-time PCR and ELISA analysis revealed that 10μg/mL of hucMSC-derived exosomes significantly inhibited the release of interleukin-6 (IL-6) and interleukin-1 beta (IL-1β) and increased tumor necrosis factor alpha (TNFA) in injured EECs. In addition, 10μg/mL of hucMSC-derived exosomes significantly inhibited toll-like receptor 4 (TLR4) and v-rel reticuloendotheliosis viral oncogene homolog A (RelA) expression in injured EECs. In OGD/R-induced injured EECs, hucMSC-derived exosomes efficiently improved the cell viability, reduced cell death, and exhibited anti-inflammatory properties against OGD/R.