The incidence of premature ovarian failure (POF), a condition causing amenorrhea and hypergonadotropic hypoestrogenism in women before the age of 40, has been increasing in recent years. As an irreversible pathological change, improved treatment strategies for this disease are urgently needed. In this study, a type of microRNA (miR-17-3p) was used to guide the differentiation of human-induced pluripotent stem (iPS) cells into hormone-sensitive ovarian epithelial (OSE)-like cells in vitro. To prevent their morphological transformation into fibroblast-like cells, MiR-17-3p, a microRNA that suppresses vimentin expression, was transfected into human iPS cells. Subsequently, these cells were successfully induced into OSE-like cells in vitro after treatment with estrogen and cell growth factors. Compared with controls, iPS cells transfected with miR-17-3p expressed higher levels of epithelial markers (cytokeratin 7, AE1, AE3, and E-cadherin) and estrogen receptors (ER and ER) while levels of mesenchymal markers (fibronectin, vimentin, and N-cadherin) lowered after the induction. The human iPS cell-derived OSE-like cells were then injected into cyclophosphamide-induced POF model mice to determine their potential benefit as grafts to repair ovarian tissues. The OSE-like cells survived within POF mouse ovaries for at least 14 days in vivo. Compared with the negative controls, expressions of cytokeratin 7 and ER proteins were elevated while fibronectin and vimentin levels in ovarian tissues were downregulated in the OSE-like cell transplantation group. Moreover, the ovarian weight and plasma E-2 level increased over time in the transplantation with OSE-like cells, compared with control groups. Hence, we can draw the conclusion that iPS cells can be induced to differentiate into OSE-like cells in vitro.
[1]Shanghai Univ Tradit Chinese Med, Longhua Hosp, Shanghai Geriatr Inst Chinese Med, Shanghai 200031, Peoples R China.
[2]Second Mil Med Univ, Dept Med Oncol, Shanghai Changzheng Hosp, Shanghai 200070, Peoples R China.
[3]Tongji Univ, Sch Life Sci & Technol, Shanghai 200092, Peoples R China.
[4]Shanghai Jiao Tong Univ, Shanghai Key Lab Stomatol, Dept Oral & Craniomaxillofacial Sci, Sch Med,Shanghai Peoples Hosp 9, Shanghai 200030, Peoples R China.
(8.0+极速模式)