BACKGROUND Extracellular vesicles derived from mesenchymal stromal cells(MSC-EVs)can be used for anti-aging therapy and treating various aging-related diseases.However,the clinical application of MSC-EVs is still limi...BACKGROUND Extracellular vesicles derived from mesenchymal stromal cells(MSC-EVs)can be used for anti-aging therapy and treating various aging-related diseases.However,the clinical application of MSC-EVs is still limited,mainly due to insufficient in-formation on the preparation process,quality,and mechanism of action of MSC-EVs.To study the biological effects of MSC-EVs in regulating cellular senescence.METHODS In this study,we developed a clinical-grade production process for MSC-EVs and defined the release criteria for products suitable for human use.To support the clinical use of our product as a therapeutic agent,we performed efficacy assays to evaluate the anti-aging capacity of MSC-EVs in vitro and in vivo.RESULTS The functional analysis results revealed that MSC-EVs significantly reduced the levels of senescence-associatedβ-galactosidase,matrix metallopeptidase 1,P21,and interleukin-1βand increased the level of collagen I in a naturally aged cell model of human dermal fibroblasts.Similarly,treatment with MSC-EVs effectively improved D-gal-induced subacute aging in mice,aging-related histopathological changes,oxidative stress,and aging-related gene expression.CONCLUSION These findings indicate that MSC-EVs can partially alleviate D-gal-induced senescence by reducing oxidative stress and regulating metabolism.Overall,these findings strongly suggest that MSC-EVs hold promise for aging therapy.展开更多
BACKGROUND Mesenchymal stromal cells(MSCs)are renowned for their immunosuppressive properties,which make them widely used in managing excessive inflammation.Although CD146+and CD146-MSCs exhibit similar morphological ...BACKGROUND Mesenchymal stromal cells(MSCs)are renowned for their immunosuppressive properties,which make them widely used in managing excessive inflammation.Although CD146+and CD146-MSCs exhibit similar morphological traits and surface marker expression levels,the specific characteristics and differential regulatory mechanisms of these two subtypes remain poorly understood.This knowledge gap has limited the precise application of MSCs in targeted thera-peutic strategies.AIM To compare the functional differences between CD146+and CD146-MSCs and investigate the underlying mechanisms.METHODS In this study,magnetic beads were used to sort umbilical cord-derived MSCs into CD146+and CD146-subsets.The pro-angiogenic factors(hepatocyte growth factor,prostaglandin E2,vascular endothelial growth factor,angiopoietin-1)production and immunomodulatory effects on T lymphocyte subsets were evaluated in vitro.The therapeutic efficacy was assessed in an acute respiratory distress syndrome(ARDS)mouse model via tail vein injection.RESULTS Cytokine secretion and angiogenesis:CD146+MSCs significantly increased the production of hepatocyte growth factor,prostaglandin E2,vascular endothelial growth factor,and angiopoietin-1 and exhibited increased pro-angiogenic activity in vitro.Immunomodulatory effects:CD146+MSCs potently inhibited the differentiation and proliferation of pro-inflammatory T helper type 1/T helper type 17 cells while promoting the expansion of regulatory T cells during T lymphocyte activation.ARDS therapy:In a mouse ARDS model,compared with CD146-MSCs,CD146+MSCs demonstrated superior therapeutic efficacy,as evidenced by improved clinical scores.Mechanistically,CD146+MSCs activated the nuclear factor kappa B pathway,upregulated cyclooxygenase 2 expression,and facilitated damaged epithelial cell repair.CONCLUSION CD146+MSCs show stronger ARDS therapeutic potential than CD146-MSCs via pro-angiogenic/immunomodulatory traits.Nuclear factor kappa B/cyclooxygenase 2 activation aids epithelial repair,highlighting CD146+MSCs as promising targets.展开更多
基金Supported by the Ministry of Science and Technology of China,No.2021YFA1101502。
文摘BACKGROUND Extracellular vesicles derived from mesenchymal stromal cells(MSC-EVs)can be used for anti-aging therapy and treating various aging-related diseases.However,the clinical application of MSC-EVs is still limited,mainly due to insufficient in-formation on the preparation process,quality,and mechanism of action of MSC-EVs.To study the biological effects of MSC-EVs in regulating cellular senescence.METHODS In this study,we developed a clinical-grade production process for MSC-EVs and defined the release criteria for products suitable for human use.To support the clinical use of our product as a therapeutic agent,we performed efficacy assays to evaluate the anti-aging capacity of MSC-EVs in vitro and in vivo.RESULTS The functional analysis results revealed that MSC-EVs significantly reduced the levels of senescence-associatedβ-galactosidase,matrix metallopeptidase 1,P21,and interleukin-1βand increased the level of collagen I in a naturally aged cell model of human dermal fibroblasts.Similarly,treatment with MSC-EVs effectively improved D-gal-induced subacute aging in mice,aging-related histopathological changes,oxidative stress,and aging-related gene expression.CONCLUSION These findings indicate that MSC-EVs can partially alleviate D-gal-induced senescence by reducing oxidative stress and regulating metabolism.Overall,these findings strongly suggest that MSC-EVs hold promise for aging therapy.
基金Supported by the Science and Technology SMEs Innovation Capacity Improvement Project of Shandong Province,No.2022TSGC1004National Key R&D Program of China,No.2021YFA1101502。
文摘BACKGROUND Mesenchymal stromal cells(MSCs)are renowned for their immunosuppressive properties,which make them widely used in managing excessive inflammation.Although CD146+and CD146-MSCs exhibit similar morphological traits and surface marker expression levels,the specific characteristics and differential regulatory mechanisms of these two subtypes remain poorly understood.This knowledge gap has limited the precise application of MSCs in targeted thera-peutic strategies.AIM To compare the functional differences between CD146+and CD146-MSCs and investigate the underlying mechanisms.METHODS In this study,magnetic beads were used to sort umbilical cord-derived MSCs into CD146+and CD146-subsets.The pro-angiogenic factors(hepatocyte growth factor,prostaglandin E2,vascular endothelial growth factor,angiopoietin-1)production and immunomodulatory effects on T lymphocyte subsets were evaluated in vitro.The therapeutic efficacy was assessed in an acute respiratory distress syndrome(ARDS)mouse model via tail vein injection.RESULTS Cytokine secretion and angiogenesis:CD146+MSCs significantly increased the production of hepatocyte growth factor,prostaglandin E2,vascular endothelial growth factor,and angiopoietin-1 and exhibited increased pro-angiogenic activity in vitro.Immunomodulatory effects:CD146+MSCs potently inhibited the differentiation and proliferation of pro-inflammatory T helper type 1/T helper type 17 cells while promoting the expansion of regulatory T cells during T lymphocyte activation.ARDS therapy:In a mouse ARDS model,compared with CD146-MSCs,CD146+MSCs demonstrated superior therapeutic efficacy,as evidenced by improved clinical scores.Mechanistically,CD146+MSCs activated the nuclear factor kappa B pathway,upregulated cyclooxygenase 2 expression,and facilitated damaged epithelial cell repair.CONCLUSION CD146+MSCs show stronger ARDS therapeutic potential than CD146-MSCs via pro-angiogenic/immunomodulatory traits.Nuclear factor kappa B/cyclooxygenase 2 activation aids epithelial repair,highlighting CD146+MSCs as promising targets.
