The restorative effects of adipose-derived mesenchymal stem cells on damaged ovarian function

Abstract

The clinical application of human adipose-derived mesenchymal stem cells (MSCs) as treatment for intractable diseases or traumatic tissue damage has attracted attention. To address the ability of reactivating injured ovaries, we prepared a rat model with damaged ovaries by using an anticancer agent, cyclophosphamide (CTX). We then investigated the restorative effects on ovarian function and the safety of adipose-derived MSCs (A-MSCs). MSCs were shown to be capable of inducing angiogenesis and restoring the number of ovarian follicles and corpus lutea in ovaries. No deformities, tumor formation or deaths were observed in F1 and F2 rats, indicating that the local injection of MSCs into the ovary did not have any obvious side effects. In addition, the localization of the Y chromosome was investigated using the fluorescent in situ hybridization method by injecting male A-MSCs into the ovaries; as a result, the Y chromosomes were localized not in the follicles, but in the thecal layers. ELISA revealed that A-MSCs secreted higher levels of vascular endothelial cell growth factor (VEGF), insulin-like growth factor-1 (IGF-1) and hepatocyte growth factor (HGF) than tail fibroblast cells. Quantitative real-time PCR and immunohistochemistry showed that higher expression levels of VEGF, IGF-1 and HGF were observed in CTX-treated ovaries after A-MSC transplantation. These findings suggest that MSCs may have a role in restoring damaged ovarian function and could be useful for regenerative medicine.

Effect of stem cell application on Asherman syndrome, an experimental rat model

“…A very recent report showed that ADSCs were capable of restoring the ovarian follicles and corpus lutea after induced damage of ovaries with cyclophosphamide [29]. Consistent with our immunohistochemical findings, we found that ADSCs also were as effective as estrogen in promoting endometrial proliferation.…”

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.…”