Premature ovarian failure(POF) is a refractory disease for clinical treatment with the goal of restoring fertility. In this study,umbilical cord mesenchymal stem cells on a collagen scaffold(collagen/UC-MSCs) can acti...Premature ovarian failure(POF) is a refractory disease for clinical treatment with the goal of restoring fertility. In this study,umbilical cord mesenchymal stem cells on a collagen scaffold(collagen/UC-MSCs) can activate primordial follicles in vitro via phosphorylation of FOXO3 a and FOXO1. Transplantation of collagen/UC-MSCs to the ovaries of POF patients rescued overall ovarian function, evidenced by elevated estradiol concentrations, improved follicular development, and increased number of antral follicles. Successful clinical pregnancy was achieved in women with POF after transplantation of collagen/UC-MSCs or UC-MSCs. In summary, collagen/UC-MSC transplantation may provide an effective treatment for POF.展开更多
Keloids,characterized by excessive collagen deposition and recurrence,pose significant therapeutic challenges due to limited mechanistic understanding.Mesenchymal stem cells(MSCs)exhibit potential for keloid managemen...Keloids,characterized by excessive collagen deposition and recurrence,pose significant therapeutic challenges due to limited mechanistic understanding.Mesenchymal stem cells(MSCs)exhibit potential for keloid management,but their precise mechanisms remain unclear.This study investigated how MSCs modulate extracellular matrix(ECM)remodeling in keloid pathogenesis.Using a co-culture system of human umbilical cord MSCs(UC-MSCs)and immortalized keloid fibroblasts(HDIKFs),we demonstrated that UC-MSCs significantly suppressed HDIKF proliferation(via CCK8 assay)and migration(via wound healing assay).Interestingly,UC-MSCs did not alter keloid xenograft growth in vivo.Mechanistically,quantitative real-time reverse transcription-polymerase chain reaction(qRT-PCR)revealed selective downregulation of matrix metalloproteinases 9(MMP9)in HDIKFs co-cultured with UC-MSCs,while MMP1,MMP2,and MMP3 remained unaffected.This suppression was linked to inhibition of the transforming growth factor-β1/SMAD(TGF-β1/SMAD)pathway,evidenced by reduced hypoxia‐inducible factor-1α(HIF-1α)and SMAD2 expression,alongside upregulated interleukin-10 receptor alpha(IL-10RA).Additionally,UC-MSCs did not alter collagen Ⅰ/Ⅲ(COL Ⅰ/Ⅲ)ratios or phosphatidylinositol‐3‐kinase(PI3K)/protein kinase B(AKT)signaling.These findings highlight that MSCs attenuate keloid fibroblast activity through TGF-β1/SMAD-driven MMP9 suppression and IL-10RA enhancement,offering novel insights into MSC-based strategies for ECM homeostasis.This study underscores MMP9 as a therapeutic target and provides a foundation for refining MSC efficacy in keloid treatment.展开更多
基金supported by Strategic Priority Research Program of the Chinese Academy of Sciences (XDA01030501 to Haixiang Sun)National Natural Science Foundation of China (31571189, 81571391, 30900847 to Lijun Ding)+1 种基金Jiangsu Provincial Medical Youth Talent (QNRC2016006)Nanjing Medical Science Development Project (JQX14004, ZKX16042)
文摘Premature ovarian failure(POF) is a refractory disease for clinical treatment with the goal of restoring fertility. In this study,umbilical cord mesenchymal stem cells on a collagen scaffold(collagen/UC-MSCs) can activate primordial follicles in vitro via phosphorylation of FOXO3 a and FOXO1. Transplantation of collagen/UC-MSCs to the ovaries of POF patients rescued overall ovarian function, evidenced by elevated estradiol concentrations, improved follicular development, and increased number of antral follicles. Successful clinical pregnancy was achieved in women with POF after transplantation of collagen/UC-MSCs or UC-MSCs. In summary, collagen/UC-MSC transplantation may provide an effective treatment for POF.
基金supported by the grants from the CAMS Innovation Fund for Medical Science(2021-I2M-1-019 to Y.G.and W.Z.,2023-I2M-2-007 to Y.G.,and 2024-I2M-ZD-010 to Y.G.)the National Natural Science Foundation of China(82370120 to Y.L.,92068204 to Y.G.,and 82200126 to W.Z.)+1 种基金Young Scientific and Technological Talents(Level Two)in Tianjin(QN20230216 to Y.L.)a SKLEH-Pilot Research Grant。
文摘Keloids,characterized by excessive collagen deposition and recurrence,pose significant therapeutic challenges due to limited mechanistic understanding.Mesenchymal stem cells(MSCs)exhibit potential for keloid management,but their precise mechanisms remain unclear.This study investigated how MSCs modulate extracellular matrix(ECM)remodeling in keloid pathogenesis.Using a co-culture system of human umbilical cord MSCs(UC-MSCs)and immortalized keloid fibroblasts(HDIKFs),we demonstrated that UC-MSCs significantly suppressed HDIKF proliferation(via CCK8 assay)and migration(via wound healing assay).Interestingly,UC-MSCs did not alter keloid xenograft growth in vivo.Mechanistically,quantitative real-time reverse transcription-polymerase chain reaction(qRT-PCR)revealed selective downregulation of matrix metalloproteinases 9(MMP9)in HDIKFs co-cultured with UC-MSCs,while MMP1,MMP2,and MMP3 remained unaffected.This suppression was linked to inhibition of the transforming growth factor-β1/SMAD(TGF-β1/SMAD)pathway,evidenced by reduced hypoxia‐inducible factor-1α(HIF-1α)and SMAD2 expression,alongside upregulated interleukin-10 receptor alpha(IL-10RA).Additionally,UC-MSCs did not alter collagen Ⅰ/Ⅲ(COL Ⅰ/Ⅲ)ratios or phosphatidylinositol‐3‐kinase(PI3K)/protein kinase B(AKT)signaling.These findings highlight that MSCs attenuate keloid fibroblast activity through TGF-β1/SMAD-driven MMP9 suppression and IL-10RA enhancement,offering novel insights into MSC-based strategies for ECM homeostasis.This study underscores MMP9 as a therapeutic target and provides a foundation for refining MSC efficacy in keloid treatment.
