Transplantation of UC-MSCs on collagen scaffold activates follicles in dormant ovaries of POF patients with long history of infertility
Premature ovarian failure (POF) is a refractory disease for clinical treatment with the goal of restoring fertility. In this study, umbilical cord mesenchymal stem cells on a collagen scaffold (collagen/UC-MSCs) can activate primordial follicles in vitro via phosphorylation of FOXO3a and FOXO1. Transplantation of collagen/UC-MSCs to the ovaries of POF patients rescued overall ovarian function, evidenced by elevated estradiol concentrations, improved follicular development, and increased number of antral follicles. Successful clinical pregnancy was achieved in women with POF after transplantation of collagen/UC-MSCs or UC-MSCs. In summary, collagen/UC-MSC transplantation may provide an effective treatment for POF.
Keywordspremature ovarian failure collagen scaffold UC-MSCs primordial follicle activation granulosa cells FOXO3a FOXO1
The authors would like to thank Xiaoling Sun, Yong Liu and Fangfang He for their technical assistance in TVUS-guided transplantation, flow cytometry and repeated transvaginal ultrasonographic examinations, respectively. This work was supported by Strategic Priority Research Program of the Chinese Academy of Sciences (XDA01030501 to Haixiang Sun), National Natural Science Foundation of China (31571189, 81571391, 30900847 to Lijun Ding), Jiangsu Provincial Medical Youth Talent (QNRC2016006) and Nanjing Medical Science Development Project (JQX14004, ZKX16042).
- Elfayomy, A.K., Almasry, S.M., El-Tarhouny, S.A., and Eldomiaty, M.A. (2016). Human umbilical cord blood-mesenchymal stem cells transplantation renovates the ovarian surface epithelium in a rat model of premature ovarian failure: possible direct and indirect effects. Tissue Cell 48, 370–382.CrossRefGoogle Scholar
- Esmaielzadeh, F., Hosseini, S.M., Nasiri, Z., Hajian, M., Chamani, M., Gourabi, H., Shahverdi, A.H., Vosough, A.D., and Nasr-Esfahani, M.H. (2013). Kit ligand and glial-derived neurotrophic factor as alternative supplements for activation and development of ovine preantral follicles in vitro. Mol Reproduct Dev 80, 35–47.CrossRefGoogle Scholar
- Wimmer, R.J., Liu, Y., Schachter, T.N., Stonko, D.P., Peercy, B.E., and Schneider, M.F. (2014). Mathematical modeling reveals modulation of both nuclear influx and efflux of Foxo1 by the IGF-I/PI3K/Akt pathway in skeletal muscle fibers. Am J Physiol Cell Physiol 306, C570–C584.CrossRefGoogle Scholar