title: 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.
authors.affiliation: The Center of Research Laboratory, and Department of Gynecology, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Lai
authors.affiliation: The Center of Research Laboratory, and Department of Gynecology, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Fangyuan
authors.initials: F
authors.lastname: Wang
authors.affiliation: The Center of Research Laboratory, and Department of Gynecology, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Zhangli
authors.initials: Z
authors.lastname: Dong
authors.affiliation: The Center of Research Laboratory, and Department of Gynecology, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Qiuwan
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D018398:Homeodomain Proteins / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D060850:LIM-Homeodomain Proteins / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009866:Oogenesis / Q000502:physiology; D006080:Ovarian Follicle / Q000378:metabolism / Q000503:physiopathology; D010053:Ovary / Q000378:metabolism / Q000503:physiopathology*; D016649:Primary Ovarian Insufficiency / Q000378:metabolism / Q000503:physiopathology*; D016601:RNA-Binding Proteins / Q000378:metabolism; D012867:Skin / Q000503:physiopathology*; D014157:Transcription Factors / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; C112960:LIM homeobox protein 8; D060850:LIM-Homeodomain Proteins; C477342:Nanos3 protein, mouse; C456265:Og2x protein, mouse; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma