Linlin Liang1,2,3,4, Lu Wang1,4, Shihao Zhou5, Jingyu Li1,4, Li Meng2,4,6, Helong Zhang1,4, Chenchen Cui7,8,9,10, Cuilian Zhang11,12,13. 1. Reproductive Medicine Center, Henan Provincial People's Hospital, Zhengzhou, Henan Province, China. 2. Henan Joint International Research Laboratory of Reproductive Bioengineering, Zhengzhou, Henan Province, China. 3. Henan Key Laboratory of Stem Cell Differentiation and Modulation, Zhengzhou, Henan Province, 45003, China. 4. Reproductive Medicine Center, People's Hospital of Zhengzhou University, Zhengzhou, Henan Province, China. 5. Xinxiang Medical University, Xinxiang, Henan Province, China. 6. LA IVF Clinic, Los Angeles, CA, USA. 7. Reproductive Medicine Center, Henan Provincial People's Hospital, Zhengzhou, Henan Province, China. ccc_sry@163.com. 8. Henan Joint International Research Laboratory of Reproductive Bioengineering, Zhengzhou, Henan Province, China. ccc_sry@163.com. 9. Henan Key Laboratory of Stem Cell Differentiation and Modulation, Zhengzhou, Henan Province, 45003, China. ccc_sry@163.com. 10. Reproductive Medicine Center, People's Hospital of Zhengzhou University, Zhengzhou, Henan Province, China. ccc_sry@163.com. 11. Reproductive Medicine Center, Henan Provincial People's Hospital, Zhengzhou, Henan Province, China. luckyzcl@qq.com. 12. Henan Joint International Research Laboratory of Reproductive Bioengineering, Zhengzhou, Henan Province, China. luckyzcl@qq.com. 13. Reproductive Medicine Center, People's Hospital of Zhengzhou University, Zhengzhou, Henan Province, China. luckyzcl@qq.com.
Abstract
PURPOSE: To investigate whether exosomes derived from human umbilical cord mesenchymal stem cells (hucMSC-derived exosomes) can repair injured endometrial epithelial cells (EECs). METHODS: HucMSC-derived exosomes and mouse primary EECs were isolated and purified. EECs were exposed to oxygen and glucose deprivation for 2 h 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 24 h 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. RESULTS: Compared with the control group, 5, 10, and 15 μg/mL of hucMSC-derived exosomes significantly attenuated cell viability decrease and inhibited LDH release of injured EECs, but 1 μg/mL of hucMSC-derived exosomes had no effect on either cell viability or LDH release. Real-time PCR and ELISA analysis revealed that 10 μg/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, 10 μg/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. CONCLUSIONS: 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.
PURPOSE: To investigate whether exosomes derived from human umbilical cord mesenchymal stem cells (hucMSC-derived exosomes) can repair injured endometrial epithelial cells (EECs). METHODS: HucMSC-derived exosomes and mouse primary EECs were isolated and purified. EECs were exposed to oxygen and glucose deprivation for 2 h 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 24 h 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. RESULTS: Compared with the control group, 5, 10, and 15 μg/mL of hucMSC-derived exosomes significantly attenuated cell viability decrease and inhibited LDH release of injured EECs, but 1 μg/mL of hucMSC-derived exosomes had no effect on either cell viability or LDH release. Real-time PCR and ELISA analysis revealed that 10 μg/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, 10 μg/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. CONCLUSIONS: 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.
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