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
Owing to its constant exposure to the external environment and various stimuli,skin ranks among the organs most vulnerable to manifestations of aging.Preventing and delaying skin aging has become one of the prominent ...Owing to its constant exposure to the external environment and various stimuli,skin ranks among the organs most vulnerable to manifestations of aging.Preventing and delaying skin aging has become one of the prominent research subjects in recent years.Mesenchymal stem celis(MsCs)are multipotent stem cells derived from mesoderm with high self-renewal ability and multilineage differentiation potential.MSC-derived extracellular vesicles(MSC-EVs)are nanoscale biological vesicles that facilitate intercellular communication and regulate biological behavior.Recent studies have shown that MSC-EVs have potential applications in anti-aging therapy due to their anti-inflammatory,anti-oxidative stress,and wound healing promoting abilities.This review presents the latest progress of MSC-EVs in delaying skin aging.It mainly includes the MSC-EVs promoting the proliferation and migration of keratinocytes and fibroblasts,reducing the expression of matrix metalloproteinases,resisting oxidative stress,and regulating inflammation.We then briefly discuss the recently discovered treatment methods of MSc-EVs in the field of skin anti-aging.Moreover,the advantages and limitations of EV-based treatments are also presented.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
The dermal papilla cells in hair follicles function as critical regulators of hair growth.In particular,alopecia areata(AA)is closely related to the malfunctioning of the human dermal papilla cells(hDPCs).Thus,identif...The dermal papilla cells in hair follicles function as critical regulators of hair growth.In particular,alopecia areata(AA)is closely related to the malfunctioning of the human dermal papilla cells(hDPCs).Thus,identifying the regulatory mechanism of hDPCs is important in inducing hair follicle(HF)regeneration in AA patients.Recently,growing evidence has indicated that 3 untranslated regions(3 UTR)of key genes may participate in the regulatory circuitry underlying cell differentiation and diseases through a socalled competing endogenous mechanism,but none have been reported in HF regeneration.Here,we demonstrate that the 3 UTR of junctional adhesion molecule A(JAM-A)could act as an essential competing endogenous RNA to maintain hDPCs function and promote HF regeneration in AA.We showed that the 3 UTR of JAM-A shares many microRNA(miRNA)response elements,especially miR-221–3p,with versican(VCAN)mRNA,and JAM-A 3 UTR could directly modulate the miRNA-mediated suppression of VCAN in self-renewing hDPCs.Furthermore,upregulated VCAN can in turn promote the expression level of JAM-A.Overall,we propose that JAM-A 3 UTR forms a feedback loop with VCAN and miR-221–3p to regulate hDPC maintenance,proliferation,and differentiation,which may lead to developing new therapies for hair loss.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the National Natural Science Foundation of China(Grant No.31971109)Shanghai Key Laboratory of Cell Engineering(Grant No.14DZ2272300)Peak Disciplines(Type IV)of Institutions of Higher Learning in Shanghai.The figures were created with BioRender.com.
文摘Owing to its constant exposure to the external environment and various stimuli,skin ranks among the organs most vulnerable to manifestations of aging.Preventing and delaying skin aging has become one of the prominent research subjects in recent years.Mesenchymal stem celis(MsCs)are multipotent stem cells derived from mesoderm with high self-renewal ability and multilineage differentiation potential.MSC-derived extracellular vesicles(MSC-EVs)are nanoscale biological vesicles that facilitate intercellular communication and regulate biological behavior.Recent studies have shown that MSC-EVs have potential applications in anti-aging therapy due to their anti-inflammatory,anti-oxidative stress,and wound healing promoting abilities.This review presents the latest progress of MSC-EVs in delaying skin aging.It mainly includes the MSC-EVs promoting the proliferation and migration of keratinocytes and fibroblasts,reducing the expression of matrix metalloproteinases,resisting oxidative stress,and regulating inflammation.We then briefly discuss the recently discovered treatment methods of MSc-EVs in the field of skin anti-aging.Moreover,the advantages and limitations of EV-based treatments are also presented.
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supported by the National Natural Science Foundation of China(Grants No.81772075,81772076,and 32071186).
文摘The dermal papilla cells in hair follicles function as critical regulators of hair growth.In particular,alopecia areata(AA)is closely related to the malfunctioning of the human dermal papilla cells(hDPCs).Thus,identifying the regulatory mechanism of hDPCs is important in inducing hair follicle(HF)regeneration in AA patients.Recently,growing evidence has indicated that 3 untranslated regions(3 UTR)of key genes may participate in the regulatory circuitry underlying cell differentiation and diseases through a socalled competing endogenous mechanism,but none have been reported in HF regeneration.Here,we demonstrate that the 3 UTR of junctional adhesion molecule A(JAM-A)could act as an essential competing endogenous RNA to maintain hDPCs function and promote HF regeneration in AA.We showed that the 3 UTR of JAM-A shares many microRNA(miRNA)response elements,especially miR-221–3p,with versican(VCAN)mRNA,and JAM-A 3 UTR could directly modulate the miRNA-mediated suppression of VCAN in self-renewing hDPCs.Furthermore,upregulated VCAN can in turn promote the expression level of JAM-A.Overall,we propose that JAM-A 3 UTR forms a feedback loop with VCAN and miR-221–3p to regulate hDPC maintenance,proliferation,and differentiation,which may lead to developing new therapies for hair loss.
