Exosomes derived from human umbilical cord mesenchymal stem cells repair injured endometrial epithelial cells
- 5 Downloads
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 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.
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.
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.
KeywordsExosome Human umbilical cord mesenchymal stem cells Endometrial epithelial cells Injury
This research was financially supported by the Key Science and Technology Program of Henan Province (182102310129) and Clinical Medicine Special Funds for Scientific Research Projects of Chinese Medical Association (18010320761).
Compliance with ethical standards
All procedures were approved by the Animal Care and Experiments of Zhengzhou University, China.
Conflict of interest
The authors declare that they have no conflict of interest.
- 7.Hong KH, Forman EJ, Werner MD, Upham KM, Gumeny CL, Winslow AD, et al. Endometrial infusion of human chorionic gonadotropin at the time of blastocyst embryo transfer does not impact clinical outcomes: a randomized, double-blind, placebo-controlled trial. Fertil Steril. 2014;102(6):1591–5.e2. https://doi.org/10.1016/j.fertnstert.2014.08.006.CrossRefPubMedGoogle Scholar
- 8.Wirleitner B, Schuff M, Vanderzwalmen P, Stecher A, Okhowat J, Hradecký L, et al. Intrauterine administration of human chorionic gonadotropin does not improve pregnancy and life birth rates independently of blastocyst quality: a randomised prospective study. Reprod Biol Endocrinol. 2015;13(1):70. https://doi.org/10.1186/s12958-015-0069-1.CrossRefPubMedPubMedCentralGoogle Scholar
- 9.Barad DH, Yu Y, Kushnir VA, Shohat-Tal A, Lazzaroni E, Lee HJ, et al. A randomized clinical trial of endometrial perfusion with granulocyte colony-stimulating factor in in vitro fertilization cycles: impact on endometrial thickness and clinical pregnancy rates. Fertil Steril. 2014;101(3):710–5. https://doi.org/10.1016/j.fertnstert.2013.12.016.CrossRefPubMedGoogle Scholar
- 11.Cervelló I, Santamaria X, Pellicer A, Remohí J, Simón C, Ferro J, et al. Autologous cell therapy with CD133+ bone marrow-derived stem cells for refractory Asherman’s syndrome and endometrial atrophy: a pilot cohort study. Hum Reprod. 2016;31(5):1087–96. https://doi.org/10.1093/humrep/dew042.CrossRefPubMedGoogle Scholar
- 13.Cao Y, Sun H, Zhu H, Zhu X, Tang X, Yan G, et al. Allogeneic cell therapy using umbilical cord MSCs on collagen scaffolds for patients with recurrent uterine adhesion: a phase I clinical trial. Stem Cell Res Ther. 2018;9(1):192. https://doi.org/10.1186/s13287-018-0904-3.CrossRefPubMedPubMedCentralGoogle Scholar
- 16.Goolaerts A, Pellan-Randrianarison N, Larghero J, Vanneaux V, Uzunhan Y, Gille T, et al. Conditioned media from mesenchymal stromal cells restore sodium transport and preserve epithelial permeability in an in vitro model of acute alveolar injury. Am J Phys Lung Cell Mol Phys. 2014;306(11):L975–85. https://doi.org/10.1152/ajplung.00242.2013.CrossRefGoogle Scholar
- 18.Zhang S, Chuah SJ, Lai RC, Hui JHP, Lim SK, Toh WS. MSC exosomes mediate cartilage repair by enhancing proliferation, attenuating apoptosis and modulating immune reactivity. Biomaterials. 2018;156:16–27. https://doi.org/10.1016/j.biomaterials.2017.11.028.CrossRefPubMedGoogle Scholar
- 19.Thomi G, Surbek D, Haesler V, Joerger-Messerli M, Schoeberlein A. Exosomes derived from umbilical cord mesenchymal stem cells reduce microglia-mediated neuroinflammation in perinatal brain injury. Stem Cell Res Ther. 2019;10(1):105. https://doi.org/10.1186/s13287-019-1207-z.CrossRefPubMedPubMedCentralGoogle Scholar
- 24.Ma Y, Dong L, Zhou D, Li L, Zhang W, Zhen Y, et al. Extracellular vesicles from human umbilical cord mesenchymal stem cells improve nerve regeneration after sciatic nerve transection in rats. J Cell Mol Med. 2019;23(4):2822–35. https://doi.org/10.1111/jcmm.14190.CrossRefPubMedPubMedCentralGoogle Scholar
- 26.Sun L, Li D, Song K, Wei J, Yao S, Li Z, et al. Exosomes derived from human umbilical cord mesenchymal stem cells protect against cisplatin-induced ovarian granulosa cell stress and apoptosis in vitro. Sci Rep. 2017;7(1):2552. https://doi.org/10.1038/s41598-017-02786-x.CrossRefPubMedPubMedCentralGoogle Scholar
- 28.Anderson JD, Johansson HJ, Graham CS, Vesterlund M, Pham MT, Bramlett CS, et al. Comprehensive proteomic analysis of mesenchymal stem cell exosomes reveals modulation of angiogenesis via nuclear factor-kappa B signaling. Stem Cells. 2016;34(3):601–13. https://doi.org/10.1002/stem.2298.CrossRefPubMedPubMedCentralGoogle Scholar
- 29.Baglio SR, Rooijers K, Koppers-Lalic D, Verweij FJ, Pérez Lanzón M, Zini N, et al. Human bone marrow- and adipose-mesenchymal stem cells secrete exosomes enriched in distinctive miRNA and tRNA species. Stem Cell Res Ther. 2015;6(1):127. https://doi.org/10.1186/s13287-015-0116-z.CrossRefPubMedPubMedCentralGoogle Scholar
- 30.Arslan F, Lai RC, Smeets MB, Akeroyd L, Choo A, Aguor ENE, et al. Mesenchymal stem cell-derived exosomes increase ATP levels, decrease oxidative stress and activate PI3K/Akt pathway to enhance myocardial viability and prevent adverse remodeling after myocardial ischemia/reperfusion injury. Stem Cell Res. 2013;10(3):301–12. https://doi.org/10.1016/j.scr.2013.01.002.CrossRefPubMedGoogle Scholar
- 31.Zhou Y, Xu H, Xu W, Wang B, Wu H, Tao Y, et al. Exosomes released by human umbilical cord mesenchymal stem cells protect against cisplatin-induced renal oxidative stress and apoptosis in vivo and in vitro. Stem Cell Res Ther. 2013;4(2):34. https://doi.org/10.1186/scrt194.CrossRefPubMedPubMedCentralGoogle Scholar