CD44+/CD105+ Human Amniotic Fluid Mesenchymal Stem Cells Survive and Proliferate in the Ovary Long-Term in a Mouse Model of Chemotherapy-Induced Premature Ovarian Failure

Abstract

Objectives: Stem cell transplantation has been reported to rescue ovarian function in a preclinical mouse model of chemotherapy-induced premature ovarian failure (POF); however, maintaining the survival and self-renewal of transplanted seed cells in ovarian tissues over the long-term remains a troublesome issue. In this study we aimed to determine whether the CD44+/CD105+ human amniotic fluid cell (HuAFCs) subpopulation represent potential seed cells for stem cell transplantation treatments in POF. Materials and methods: The CD44+/CD105+ subpopulation were isolated from HuAFCs, cultured in vitro, and injected into a cyclophosphamide-induced mouse model of POF. Results: Under continuous subculture in vitro, CD44+/CD105+ cells proliferated rapidly and expressed high levels of the proliferative markers Ki67 and survivin, as well as high levels of a number of mesenchymal stem cell biomarkers. Moreover, when red fluorescence protein (RFP)-transduced CD44+/CD105+ HuAFCs were transplanted into the ovaries of POF mice, the cells could be detected by fluorescence microscopy up to three weeks after injection. Furthermore, the BrdUrd incorporation assay and immunofluorescent staining demonstrated that CD44+/CD105+ HuAFCs underwent normal cycles of cell proliferation and self-renewal in the ovarian tissues of POF mice over the long-term. Conclusions: The mesenchymal stem cell properties and long-term in vivo survival of CD44+/CD105+ HuAFCs make them ideal seed cells for stem cell transplantation to treat POF.

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

“…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.…”

Tripterygium glycosides induce premature ovarian failure in rats by promoting p53 phosphorylation and activating the serine/threonine kinase 11-p53-p21 signaling pathway

“…These patients also exhibit symptoms of the menopause, such as hot flushes, night sweats and vaginal dryness (1)(2)(3)(4)(5). Furthermore, patients with POF are usually infertile due to a lack of mature, healthy follicles or as a result of the remaining follicles not responding to stimulation (1)(2)(3)(4)(5); therefore, POF is also known as primary ovarian insufficiency (1)(2)(3)(4)(5). At present, the number of patients with POF is increasing; however, the factors contributing to POF are largely unknown.…”

“…Premature ovarian failure (POF) is a typical pathological disease of the reproductive system in aging females (1)(2)(3)(4)(5). Patients with POF are <40 years old and commonly have the features of amenorrhea, hypoestrogenism and high levels of gonadotrophin (1)(2)(3)(4)(5).…”