Human Menstrual Blood-Derived Stromal Cells Promote Recovery of Premature Ovarian Insufficiency Via Regulating the ECM-Dependent FAK/AKT Signaling

Abstract

POI is characterized by “absent not abnormal” menstruation with hormonal disorders in woman younger than 40 years of age, and etiological and pathophysiological mechanisms underlying the POI development have not been clearly defined. Recently, due to advantages such as abundant sources and non-invasive methods of harvest, MenSCs have been emerging as a promising treatment strategy for the recovery of female reproductive damage. Here, we demonstrated that MenSCs graft in POI mice after CTX treatment could restore ovarian function by regulating normal follicle development and estrous cycle, reducing apoptosis in ovaries to maintain homeostasis of microenvironment and modulating serum sex hormones to a relatively normal status. Moreover, MenSCs participated in the activation of ovarian transcriptional expression in ECM-dependent FAK/AKT signaling pathway and thus restored ovarian function to a certain extent. MenSCs transplantation was proved to be an effective way to repair ovarian function with low immunogenicity, suggesting its great potential for POI treatment. Electronic supplementary material The online version of this article (10.1007/s12015-018-9867-0) contains supplementary material, which is available to authorized users.

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

“…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). More importantly, mated mice grafted with MenSCs had more live births indicating the potential of MenSC to repair ovarian function (Feng et al, 2019). Mechanistic analyses revealed that mice treated with MenSCs improved ovarian microenvironment homeostasis through regulation of the ECM-dependent FAK/AKT signaling pathway (Feng et al, 2019).…”

“…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.…”

Recent trends in stem cell therapy for premature ovarian insufficiency and its therapeutic potential: a review

“…Jalalie et al reported the successful engraftment of MenSCs extracted from women aged 25~35 in a CTX-induced POI mouse model; these implanted cells inhibited apoptosis and cell cycle arrest through the ECM-dependent FAK-AKT signaling pathway. Further studies are necessary to identify possible differences in MenSCs between normal donors and POI patients [6].…”

“…4x10 6 hADMSCs IP injection [28] BMMSC, OSC ■ The in-vivo transplantation of OSCs can be more effective protectors than BMMSCs for follicle maturation after chemotherapy. Unfortunately, the 2 × 10 6 BMMSCs and OSSCs injected intraperitoneally [44] lentiviral vector to overexpress miR-21 showed increased viability, and the ovulation rate increased after transplantation of these cells in rats [52].…”

“…The advantages of MSCs are that they do not raise any ethical concerns, they have low immunogenicity and limited immunomodulatory function, and they undergo chemotaxis in wound healing. However, the self-renewal potential is limited by donor age and the invasive collection methods, including bone marrow aspiration and liposuction [6].…”