The effects of human menstrual blood stem cells‐derived granulosa cells on ovarian follicle formation in a rat model of premature ovarian failure

Abstract

Many studies have reported that human endometrial mesenchymal stem cells (HuMenSCs) are capable of repairing damaged tissues. The aim of the present study was to investigate the effects of HuMenSCs transplantation as a treatment modality in premature ovarian failure (POF) associated with chemotherapy‐induced ovarian damage. HuMenSCs were isolated from menstrual blood samples of five women. After the in vitro culture of HuMenSCs, purity of the cells was assessed by cytometry using CD44, CD90, CD34, and CD45 FITC conjugate antibody. Twenty‐four female Wistar rats were randomly divided into four groups: negative control, positive control, sham, and treatment groups. The rat models of POF used in our study were established by injecting busulfan intraperitoneally into the rats during the first estrus cycle. HuMenSCs were transplanted by injection via the tail vein into the POF‐induced rats. Four weeks after POF induction, ovaries were collected and the levels of Amh, Fst, and Fshr expression in the granulosa cell (GC) layer, as well as plasma estradiol (E2) and progesterone (P4) levels were evaluated. Moreover, migration and localization of DiI‐labeled HuMenSCs were detected, and the labeled cells were found to be localized in GCs layer of immature follicles. In addition to DiI‐labelled HuMenSCs tracking, increased levels of expression of Amh and Fshr and Fst, and the high plasma levels of E2 and P4 confirmed that HuMenSC transplantation had a significant effect on follicle formation and ovulation in the treatment group compared with the negative control (POF) group.

Human mesenchymal stem cell treatment of premature ovarian failure: new challenges and opportunities

“…hMB-MSCs improved hormone secretion in rats with POF (e.g., AMH, FSHR, FST, E2, and P4). hMB-MSC transplantation not only changed ovarian ultrastructure but also improved ovarian function [131].…”

Endometrial and Menstrual Blood Mesenchymal Stem/Stromal Cells: Biological Properties and Clinical Application

“…Increased numbers of primary, mature and total ovarian follicle numbers were observed. DiI-labeled MenSC localized to GCs of immature ovarian follicles (Manshadi et al, 2019). Microarray analysis revealed greater similarity between mRNA expression patterns in the ovarian cells posttransplantation and human ovarian tissue than the pre-transplantation pattern in MenSCs, suggesting transdifferentiation into ovarian cells or fusion of MenSCs with murine cells (Liu et al, 2014).…”

“…The reparative capacities of MenSCs was exploited to treat premature ovarian failure (POF) in mouse/rat models (Liu et al, 2014;Feng et al, 2019;Manshadi et al, 2019;Yan et al, 2019). Intra-ovarian or intravenous injection of MenSCs reduced apoptosis and restored ovarian function, shown by expression of the ovarian markers, follicle-stimulating hormone receptor (Fshr), inhibin α/β, anti-Müllerian hormone (Amh), Ddx4 and Vegfa, and rising plasma levels of the ovarian hormones, estrogen and progesterone.…”

Mesenchymal Stem Cells as a Bio Organ for Treatment of Female Infertility

“…Remarkably, some studies have reported a protective role of MenSCs against GCs death in the ovarian interstitium of an animal model of POF. In these studies, MenSCs restored ovarian function [ 80 , 81 ]. It was suggested that this effect is likely mediated by a decrease in the expression of growth arrest and DNA damage inducible beta (GADD45B), a stress sensor involved in cell cycle control, and by an increase in the expression of cell division control 2 (CDC2) and cyclin B1 as cell cycle inducers [ 82 , 83 , 84 , 85 ].…”