Skin-Derived Mesenchymal Stem Cells Help Restore Function to Ovaries in a Premature Ovarian Failure Mouse Model

Abstract

Skin-derived mesenchymal stem cells (SMSCs) can differentiate into the three embryonic germ layers. For this reason, they are considered a powerful tool for therapeutic cloning and offer new possibilities for tissue therapy. Recent studies showed that skin-derived stem cells can differentiate into cells expressing germ-cell specific markers in vitro and form oocytes in vivo. The idea that SMSCs may be suitable for the treatment of intractable diseases or traumatic tissue damage has attracted attention. To determine the ability of SMSCs to reactivate injured ovaries, a mouse model with ovaries damaged by busulfan and cyclophosphamide was developed and is described here. Female skin-derived mesenchymal stem cells (F-SMSCs) and male skin-derived mesenchymal stem cells (M-SMSCs) from red fluorescence protein (RFP) transgenic adult mice were used to investigate the restorative effects of SMSCs on ovarian function. Significant increases in total body weight and the weight of reproductive organs were observed in the treated animals. Both F-SMSCs and M-SMSCs were shown to be capable of partially restoring fertility in chemotherapy-treated females. Immunostaining with RFP and anti-Müllerian hormone (AMH) antibodies demonstrated that the grafted SMSCs survived, migrated to the recipient ovaries. After SMSCs were administered to the treated mice, real-time PCR showed that the expression levels of pro-inflammatory cytokines TNF-α, TGF-β, IL-8, IL-6, IL-1β, and IFNγ were significantly lower in the ovaries than in the untreated controls. Consistent with this observation, expression of oogenesis marker genes Nobox, Nanos3, and Lhx8 increased in ovaries of SMSCs-treated mice. These findings suggest that SMSCs may play a role within the ovarian follicle microenvironment in restoring the function of damaged ovaries and could be useful in reproductive health.

Study of the reparative effects of menstrual-derived stem cells on premature ovarian failure in mice

“…Previous studies have shown that MSCs can be isolated from many tissues, including skin [37], adipose tissue [10], human amniotic fluid [38], the umbilical cord [39], and the heart [40]. MSCs have become an excellent source of seed cells that can be used for regenerative therapies in a variety of diseases because they have strong self-renewal and multi-differentiation capacities.…”

Mechanism for the Decision of Ovarian Surface Epithelial Stem Cells to Undergo Neo-Oogenesis or Ovarian Tumorigenesis

“…For example, resveratrol restores ovarian function through inhibiting NF-κB and reducing ovarian inflammation through IL-6 and IL-8 expression [136,137]. Interestingly, recent work has postulated that immune cells and their secreted inflammatory factors follow mechanics to regulate the proliferation and differentiation of ovarian germline stem cells [48,138]. First, immunity may be a part of the OSC niche.…”

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

“…Previous studies have shown that MSCs secrete cytokinins, hence, they have a positive effect on proliferation, survival and repair of damaged tissues (Cheng et al, 2013;Ding et al, 2014;Fujita et al, 2004;Wang et al, 2017). Many other previous studies have reported that MSCs implanted into damaged tissues can induce the secretion of bioactive molecules which promote repair of damaged tissues (Lai et al, 2015;Lai, Wang, Dong, & Zhang, 2014;Ranganath, Levy, Inamdar, & Karp, 2012;Schächinger et al, 2006). Likewise, Wang et al (2017) showed that MenSC-derived conditioned media has a significant cytoprotective and anti-apoptotic properties.…”