The Therapeutic Potential of Umbilical Cord Mesenchymal Stem Cells in Mice Premature Ovarian Failure

Abstract

Mesenchymal stem cells, which are poorly immunogenic and have potent immunosuppressive activities, have emerged as promising cellular therapeutics for the treatment of several diseases. Mesenchymal-like cells derived from Wharton's Jelly, called umbilical cord matrix stem cells (UCMSCs), reportedly secrete a variety of cytokines and growth factors, acting as trophic suppliers. Here, we used UCMSCs to treat premature ovarian failure (POF). Ovarian function was evaluated by ovulation and the number of follicles. Apoptosis of the granulosa cells (GC) was analyzed by TUNEL staining. We found that after transplantation of the UCMSCs, apoptosis of cumulus cells in the ovarian damage model was reduced and the function of the ovary had been recovered. The sex hormone level was significantly elevated in mice treated with UCMSCs. The number of follicles in the treated group was higher than in the control group. Our results demonstrate that UCMSCs can effectively restore ovary functionality and reduce apoptosis of granulosa cells. We compared the RNA expression of the UCMSCs treated group with the POF model and wild-type control group and found that the UCMSC group is most similar to the wild-type group. Our experiments provide new information regarding the treatment of ovarian function failure.

The protective effects of human umbilical cord mesenchymal stem cells on damaged ovarian function: A comparative study

“…hUCMSCs were prepared, identified, and cultured according to a recently published protocol (23). At passage 6, the expression of cell surface markers was analyzed with flow cytometry using fluorescein isothiocyanate (FITC)-conjugated human monoclonal antibodies such as CD14 (BioLegend, 325623), CD31 (BioLegend, 303103), CD34 (BioLegend, 343603), CD105 (BioLegend, 323203), CD45 (BioLegend, 304005), CD44 (BioLegend, 338803), CD73 (BioLegend, 344015), human leukocyte antigens-D region (HLA-DR, BioLegend, 307603), phycoerythrin (PE)-conjugated human antibodies against CD90 (BioLegend, 328109), and PE-CD29 (BioLegend, 303003).…”

“…Evidence has shown that hUCMSCs have unique advantages compared to BMSCs (22), which make them a promising source of cells for treatment. According to previous studies, stem cells to treat ovarian injury are primarily administered via intravenous injection (IV) or in situ ovarian micro injection (MI) (23)(24)(25)(26). However, very few studies have examined suitable forms of hUCMSC therapy to delay ovarian aging.…”

Putative mesenchymal stem cells isolated from adult human ovaries

“…It has already been shown in animal models that MSCs from different sources (e.g. adipose) can improve or even restore ovarian function [56][57][58][59]. To determine the ideal age at which POMSCs could be used to regenerate ovaries, the ovarian tissue of more patients at different ages would need to be included.…”

Mouse Ovarian Very Small Embryonic-Like Stem Cells Resist Chemotherapy and Retain Ability to Initiate Oocyte-Specific Differentiation

“…Few other groups have transplanted mesenchymal cells in chemoablated ovary and reported restored ovarian function. [72][73][74][75][76] All these groups have transplanted cells immediately after chemotherapy and have not waited for chemotherapy to completely destroy follicular reserve. Hence the effect appears more protective than restoration of ovarian function.…”