Human endometrial mesenchymal stem cells restore ovarian function through improving the renewal of germline stem cells in a mouse model of premature ovarian failure.

Dongmei Lai,Charlie Xiang,Xiaofen Yao,Fangyuan Wang,Qiuwan Zhang,Xiaoxing Wu

doi:10.1186/s12967-015-0516-y

Abstract

BackgroundHuman endometrial mesenchymal stem cells (EnSCs) derived from menstrual blood have mesenchymal stem/stromal cells (MSCs) characteristics and can differentiate into cell types that arise from all three germ layers. We hypothesized that EnSCs may offer promise for restoration of ovarian dysfunction associated with premature ovarian failure/insufficiency (POF/POI).MethodsMouse ovaries were injured with busulfan and cyclophosphamide (B/C) to create a damaged ovary mouse model. Transplanted EnSCs were injected into the tail vein of sterilized mice (Chemoablated with EnSCs group; n = 80), or culture medium was injected into the sterilized mice via the tail vein as chemoablated group (n = 80). Non-sterilized mice were untreated controls (n = 80). Overall ovarian function was measured using vaginal smears, live imaging, mating trials and immunohistochemical techniques.ResultsEnSCs transplantation increased body weight and improved estrous cyclicity as well as restored fertility in sterilized mice. Migration and localization of GFP-labeled EnSCs as measured by live imaging and immunofluorescent methods indicated that GFP-labeled cells were undetectable 48 h after cell transplantation, but were later detected in and localized to the ovarian stroma. 5’-bromodeoxyuridine (BrdU) and mouse vasa homologue (MVH) protein double-positive cells were immunohistochemically detected in mouse ovaries, and EnSC transplantation reduced depletion of the germline stem cell (GSCs) pool induced by chemotherapy.ConclusionEnSCs derived from menstrual blood, as autologous stem cells, may restore damaged ovarian function and offer a suitable clinical strategy for regenerative medicine.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0516-y) contains supplementary material, which is available to authorized users.

Highlights

Human endometrial mesenchymal stem cells (EnSCs) derived from menstrual blood have mesenchymal stem/stromal cells (MSCs) characteristics and can differentiate into cell types that arise from all three germ layers
Characterization of established human EnSCs Human EnSCs line was derived from menstrual blood of a 40-year-old Chinese woman [19, 23]
The number of litters obtained by natural mating was significantly increased with chemoablated with EnSCs group compared with chemoablated mice; fertility recovery was not complete compared to normal untreated controls (Fig. 4)

Summary

Introduction

Human endometrial mesenchymal stem cells (EnSCs) derived from menstrual blood have mesenchymal stem/stromal cells (MSCs) characteristics and can differentiate into cell types that arise from all three germ layers. We hypothesized that EnSCs may offer promise for restoration of ovarian dysfunction associated with premature ovarian failure/insufficiency (POF/POI). Cancer patients—especially women younger than 40 years of age—who receive chemotherapy or radiation often suffer reproductive damage. This damage is frequently associated with premature ovarian failure/insufficiency (POF/POI) and infertility due to ovarian germ cell toxicity. It is primarily believed that dormant primordial follicles were a nonrenewable population representing the “ovarian reserve” of reproductive potential [8]. Long-term maintenance of most follicles in a dormant state is important to preserve the primordial follicle stockpile and restore ovarian function during cancer treatment

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