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.
Highlights
The skin is the largest organ of the body and has long been researched as a potential source of regenerative cells
Flow cytometry was used to detect the phenotype of the 5th passage female skinderived mesenchymal stem cells (F-SMSCs) and mesenchymal stem cells (M-SMSCs)
The results showed that 96% cells of F-SMSCs or 92% cells of M-SMSCs were CD73-positive and lack of expression of CD14, CD34 and CD45 (Fig. 1E–F)
Summary
The skin is the largest organ of the body and has long been researched as a potential source of regenerative cells. Several works have shown that skin-derived multipotent stem cells are capable of differentiating into cells from the three embryonic germ layers, including neural cells, adipocytes, insulin producing cells, chondrogenic cells, and osteogenic cells [1,2,3,4,5]. Dyce et al reported that stem cells from fetal porcine skin can express germ cell markers and form oocyte-like cells in vitro [6,7] They demonstrated that newborn mouse skinderived stem cells are capable of differentiating into oocyte-like cells and forming oocytes after transplantation of cell aggregates into immunodeficient mice [8]. These findings suggest that skinderived stem cells can differentiate into germ cells and this may be useful for anti-aging treatment
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