Mesenchymal stem cells （MSCs） derived from bone marrow are a well-characterized population of adult stem cells that can be maintained and propagated in culture for a long time with the capacity to form a variety of ...Mesenchymal stem cells （MSCs） derived from bone marrow are a well-characterized population of adult stem cells that can be maintained and propagated in culture for a long time with the capacity to form a variety of cell types. This study investigated the characteristics of dairy goat bone marrow MSCs （gMSCs） and their differentiation potential toward germ cells in vitro, and to test their potential in vivo, these ceils were transplanted into seminiferous tubes of endogenous germ cells-depleted mouse models. The results showed that characteristic gMSC lines were established and a small population of gMSCs transdifferentiated into male germ cell-like cells which expressed Stra8 after induction with retinoic acid （RA）, as analysed by reverse transcription-polymerase chain reaction （RT-PCR） and immunofluorescence. Further, we transplanted the gMSCs into endogenous germ cells-depleted mouse models. A variety of analysis demonstrated that gMSCs might differentiate into male germ cells and helped spermatogenesis in endogenous germ cells depleted mouse models at 30 d after transplantation. The gMSCs could be used as a potential source of cells for reproductive studies and a neoadjuvant therapy for the spermatogenesis anomaly. Moreover, these cells may offer a new strategy for male infertility and an alternative approach for production of transgenic animals.展开更多
Background:Gingiva-derived mesenchymal stem cells(GMSCs)suppress immune and inflammatory responses in experimental arthritis models.Here,we determined whether GMSCs suppress the proliferation and invasion of rheumatoi...Background:Gingiva-derived mesenchymal stem cells(GMSCs)suppress immune and inflammatory responses in experimental arthritis models.Here,we determined whether GMSCs suppress the proliferation and invasion of rheumatoid arthritis fibroblast-like synoviocytes(RA FLSs).Methods:Surface markers of GMSCs were analyzed by flow cytometry.mRNA expression of matrix metalloproteinases and pro-inflammatory cytokine in RA FLSs was measured by quantitative polymerase chain reaction(PCR).RA FLS proliferation was analyzed by a 5-ethynyl-2′-deoxyuridine assay.To explore the molecular mechanisms,we assessed the effect of GMSCs on RA FLS proliferation by adding indoleamine-2,3-dioxygenase(IDO),CD39,or CD73 inhibitors.The invasion was analyzed by a transwell assay.The anti-inflammatory effects of GMSCs were assessed in a typeⅡcollagen-induced arthritis(CIA)mouse model.Results:Compared with human dermal fibroblast,GMSCs displayed a higher expression of CD39.Interleukin(IL)-8,IL-6,MMP-1,MMP-3,MMP-13,and monocyte chemoattractant protein-1 mRNA were all decreased in RA FLSs after incubation with GMSCs.GMSCs significantly reduced RA FLS proliferation in a dose-dependent manner in vitro,which was partly dependent on CD39/CD73 signaling.GMSCs significantly impeded the invasive capacity of RA FLSs in a dose-dependent manner in vitro.GMSCs infusion delayed arthritis onset and reduced arthritis scores in the CIA model.Conclusion:GMSCs are effective to inhibit the aggressive behavior of RA FLSs and treat experimental arthritis,implying their therapeutic potential in RA patients.展开更多
基金supported by the grants from the National Natural Science Foundation of China(30972097)the Key Program of Ministry of Education of China (109148)+2 种基金the Proram for New Century Excellent Talents in University, China (NCET-09-0654)the Scientific Research Program of Shaanxi Province, China (2011K02-06)the China Postdoctoral Science Foundation(20080431253)
文摘Mesenchymal stem cells （MSCs） derived from bone marrow are a well-characterized population of adult stem cells that can be maintained and propagated in culture for a long time with the capacity to form a variety of cell types. This study investigated the characteristics of dairy goat bone marrow MSCs （gMSCs） and their differentiation potential toward germ cells in vitro, and to test their potential in vivo, these ceils were transplanted into seminiferous tubes of endogenous germ cells-depleted mouse models. The results showed that characteristic gMSC lines were established and a small population of gMSCs transdifferentiated into male germ cell-like cells which expressed Stra8 after induction with retinoic acid （RA）, as analysed by reverse transcription-polymerase chain reaction （RT-PCR） and immunofluorescence. Further, we transplanted the gMSCs into endogenous germ cells-depleted mouse models. A variety of analysis demonstrated that gMSCs might differentiate into male germ cells and helped spermatogenesis in endogenous germ cells depleted mouse models at 30 d after transplantation. The gMSCs could be used as a potential source of cells for reproductive studies and a neoadjuvant therapy for the spermatogenesis anomaly. Moreover, these cells may offer a new strategy for male infertility and an alternative approach for production of transgenic animals.
基金National Natural Science Foundation of China,Grant/Award Number:82171768Zhejiang Provincial Natural Science Foundation of China,Grant/Award Number:LQ17H100001。
文摘Background:Gingiva-derived mesenchymal stem cells(GMSCs)suppress immune and inflammatory responses in experimental arthritis models.Here,we determined whether GMSCs suppress the proliferation and invasion of rheumatoid arthritis fibroblast-like synoviocytes(RA FLSs).Methods:Surface markers of GMSCs were analyzed by flow cytometry.mRNA expression of matrix metalloproteinases and pro-inflammatory cytokine in RA FLSs was measured by quantitative polymerase chain reaction(PCR).RA FLS proliferation was analyzed by a 5-ethynyl-2′-deoxyuridine assay.To explore the molecular mechanisms,we assessed the effect of GMSCs on RA FLS proliferation by adding indoleamine-2,3-dioxygenase(IDO),CD39,or CD73 inhibitors.The invasion was analyzed by a transwell assay.The anti-inflammatory effects of GMSCs were assessed in a typeⅡcollagen-induced arthritis(CIA)mouse model.Results:Compared with human dermal fibroblast,GMSCs displayed a higher expression of CD39.Interleukin(IL)-8,IL-6,MMP-1,MMP-3,MMP-13,and monocyte chemoattractant protein-1 mRNA were all decreased in RA FLSs after incubation with GMSCs.GMSCs significantly reduced RA FLS proliferation in a dose-dependent manner in vitro,which was partly dependent on CD39/CD73 signaling.GMSCs significantly impeded the invasive capacity of RA FLSs in a dose-dependent manner in vitro.GMSCs infusion delayed arthritis onset and reduced arthritis scores in the CIA model.Conclusion:GMSCs are effective to inhibit the aggressive behavior of RA FLSs and treat experimental arthritis,implying their therapeutic potential in RA patients.
