Androgenic alopecia(AGA)is a highly prevalent form of non-scarring alopecia but lacks effective treatments.Stem cell exosomes have similar repair effects to stem cells,suffer from the drawbacks of high cost and low yi...Androgenic alopecia(AGA)is a highly prevalent form of non-scarring alopecia but lacks effective treatments.Stem cell exosomes have similar repair effects to stem cells,suffer from the drawbacks of high cost and low yield yet.Cell-derived nanovesicles acquired through mechanical extrusion exhibit favorable biomimetic properties similar to exosomes,enabling them to efficiently encapsulate substantial quantities of therapeutic proteins.In this study,we observed that JAM-A,an adhesion protein,resulted in a significantly increased the adhesion and resilience of dermal papilla cells to form snap structures against damage caused by dihydrotestosterone and macrophages,thereby facilitating the process of hair regrowth in cases of AGA.Consequently,adipose-derived stem cells were modified to overexpress JAM-A to produce engineered JAM-A overexpressing nanovesicles(JAM-A^(OE)@NV).The incorporation of JAM-A^(OE)@NV into a thermosensitive hydrogel matrix(JAM-A^(OE)@NV Gel)to effectively addresses the limitations associated with the short half-life of JAM-A^(OE)@NV,and resulted in the achievement of a sustained-release profile for JAM-A^(OE)@NV.The physicochemical characteristics of the JAM-A^(OE)@NV Gel were analyzed and assessed for its efficacy in promoting hair regrowth in vivo and vitro.The JAM-A^(OE)@NV Gel,thus,presents a novel therapeutic approach and theoretical framework for promoting the treatment of low cell adhesion diseases similar to AGA.展开更多
Objectives Alopecia areata(AA)is an autoimmune-related non-cicatricial alopecia,with complete alopecia(AT)or generalized alopecia(AU)as severe forms of AA.However,there are limitations in early identification of AA,an...Objectives Alopecia areata(AA)is an autoimmune-related non-cicatricial alopecia,with complete alopecia(AT)or generalized alopecia(AU)as severe forms of AA.However,there are limitations in early identification of AA,and intervention of AA patients who may progress to severe AA will help to improve the incidence rate and prognosis of severe AA.Methods We obtained two AA-related datasets from the gene expression omnibus database,identified the differentially expressed genes(DEGs),and identified the module genes most related to severe AA through weighted gene co-expression network analysis.Functional enrichment analysis,construction of a protein–protein interaction network and competing endogenous RNA network,and immune cell infiltration analysis were performed to clarify the underlying biological mechanisms of severe AA.Subsequently,pivotal immune monitoring genes(IMGs)were screened through multiple machine-learning algorithms,and the diagnostic effectiveness of the pivotal IMGs was validated by receiver operating characteristic.Results A total of 150 severe AA-related DEGs were identified;the upregulated DEGs were mainly enriched in immune response,while the downregulated DEGs were mainly enriched in pathways related to hair cycle and skin development.Four IMGs(LGR5,SHISA2,HOXC13,and S100A3)with good diagnostic efficiency were obtained.As an important gene of hair follicle stem cells stemness,we verified in vivo that LGR5 downregulation may be an important link leading to severe AA.Conclusion Our findings provide a comprehensive understanding of the pathogenesis and underlying biological processes in patients with AA,and identification of four potential IMGs,which is helpful for the early diagnosis of severe AA.展开更多
Human adipose tissue-derived stem cell(ADSC)derivatives are cell-free,with low immunogenicity and no potential tumourigenicity,making them ideal for aiding wound healing.However,variable quality has impeded their clin...Human adipose tissue-derived stem cell(ADSC)derivatives are cell-free,with low immunogenicity and no potential tumourigenicity,making them ideal for aiding wound healing.However,variable quality has impeded their clinical application.Metformin(MET)is a 5′adenosine monophosphate-activated protein kinase activator associated with autophagic activation.In this study,we assessed the potential applicability and underlying mechanisms of MET-treated ADSC derivatives in enhancing angiogenesis.We employed various scientific techniques to evaluate the influence of MET on ADSC,assess angiogenesis and autophagy in MET-treated ADSC in vitro,and examine whether MET-treated ADSC increase angiogenesis.We found that low MET concentrations exerted no appreciable effect on ADSC proliferation.However,MET was observed to enhance the angiogenic capacity and autophagy of ADSC.MET-induced autophagy was associated with increased vascular endothelial growth factor A production and release,which contributed to promoting the therapeutic efficacy of ADSC.In vivo experiments confirmed that in contrast to untreated ADSC,MET-treated ADSC promoted angiogenesis.Our findings thus indicate that the application of MET-treated ADSC would be an effective approach to accelerate wound healing by promoting angiogenesis at wound sites.展开更多
基金supported by the Featured Clinical Discipline Project of Shanghai Pudong Fund(Grant No.PWYts2021-07)the East Hospital Affiliated to Tongji University Introduced Talent Research Startup Fund(Grant No.DFRC2019008)the National Natural Science Foundation of China(Grant No.32071186).
文摘Androgenic alopecia(AGA)is a highly prevalent form of non-scarring alopecia but lacks effective treatments.Stem cell exosomes have similar repair effects to stem cells,suffer from the drawbacks of high cost and low yield yet.Cell-derived nanovesicles acquired through mechanical extrusion exhibit favorable biomimetic properties similar to exosomes,enabling them to efficiently encapsulate substantial quantities of therapeutic proteins.In this study,we observed that JAM-A,an adhesion protein,resulted in a significantly increased the adhesion and resilience of dermal papilla cells to form snap structures against damage caused by dihydrotestosterone and macrophages,thereby facilitating the process of hair regrowth in cases of AGA.Consequently,adipose-derived stem cells were modified to overexpress JAM-A to produce engineered JAM-A overexpressing nanovesicles(JAM-A^(OE)@NV).The incorporation of JAM-A^(OE)@NV into a thermosensitive hydrogel matrix(JAM-A^(OE)@NV Gel)to effectively addresses the limitations associated with the short half-life of JAM-A^(OE)@NV,and resulted in the achievement of a sustained-release profile for JAM-A^(OE)@NV.The physicochemical characteristics of the JAM-A^(OE)@NV Gel were analyzed and assessed for its efficacy in promoting hair regrowth in vivo and vitro.The JAM-A^(OE)@NV Gel,thus,presents a novel therapeutic approach and theoretical framework for promoting the treatment of low cell adhesion diseases similar to AGA.
基金supported by the National Natural Science Foundation of China(Grant No.32071186).
文摘Objectives Alopecia areata(AA)is an autoimmune-related non-cicatricial alopecia,with complete alopecia(AT)or generalized alopecia(AU)as severe forms of AA.However,there are limitations in early identification of AA,and intervention of AA patients who may progress to severe AA will help to improve the incidence rate and prognosis of severe AA.Methods We obtained two AA-related datasets from the gene expression omnibus database,identified the differentially expressed genes(DEGs),and identified the module genes most related to severe AA through weighted gene co-expression network analysis.Functional enrichment analysis,construction of a protein–protein interaction network and competing endogenous RNA network,and immune cell infiltration analysis were performed to clarify the underlying biological mechanisms of severe AA.Subsequently,pivotal immune monitoring genes(IMGs)were screened through multiple machine-learning algorithms,and the diagnostic effectiveness of the pivotal IMGs was validated by receiver operating characteristic.Results A total of 150 severe AA-related DEGs were identified;the upregulated DEGs were mainly enriched in immune response,while the downregulated DEGs were mainly enriched in pathways related to hair cycle and skin development.Four IMGs(LGR5,SHISA2,HOXC13,and S100A3)with good diagnostic efficiency were obtained.As an important gene of hair follicle stem cells stemness,we verified in vivo that LGR5 downregulation may be an important link leading to severe AA.Conclusion Our findings provide a comprehensive understanding of the pathogenesis and underlying biological processes in patients with AA,and identification of four potential IMGs,which is helpful for the early diagnosis of severe AA.
基金the National Natural Science Foundation of China(grant no.81871578)the Naval Military Medical University Basic Research Project(2022MS010)the Shanghai Municipal Commission of Health and Family Planning Clinical Research Program(20184Y0113).
文摘Human adipose tissue-derived stem cell(ADSC)derivatives are cell-free,with low immunogenicity and no potential tumourigenicity,making them ideal for aiding wound healing.However,variable quality has impeded their clinical application.Metformin(MET)is a 5′adenosine monophosphate-activated protein kinase activator associated with autophagic activation.In this study,we assessed the potential applicability and underlying mechanisms of MET-treated ADSC derivatives in enhancing angiogenesis.We employed various scientific techniques to evaluate the influence of MET on ADSC,assess angiogenesis and autophagy in MET-treated ADSC in vitro,and examine whether MET-treated ADSC increase angiogenesis.We found that low MET concentrations exerted no appreciable effect on ADSC proliferation.However,MET was observed to enhance the angiogenic capacity and autophagy of ADSC.MET-induced autophagy was associated with increased vascular endothelial growth factor A production and release,which contributed to promoting the therapeutic efficacy of ADSC.In vivo experiments confirmed that in contrast to untreated ADSC,MET-treated ADSC promoted angiogenesis.Our findings thus indicate that the application of MET-treated ADSC would be an effective approach to accelerate wound healing by promoting angiogenesis at wound sites.
