Background:Schwann cell-like cells(SCLCs),differentiated from mesenchymal stem cells,have shown promising outcomes in the treatment of peripheral nerve injuries in preclinical studies.However,certain clinical obstacle...Background:Schwann cell-like cells(SCLCs),differentiated from mesenchymal stem cells,have shown promising outcomes in the treatment of peripheral nerve injuries in preclinical studies.However,certain clinical obstacles limit their application.Hence,the primary aim of this study was to investigate the role of exosomes derived from SCLCs(SCLCs-exo)in peripheral nerve regeneration.Methods:SCLCs were differentiated from human amniotic mesenchymal stem cells(hAMSCs)in vitro and validated by immunofluorescence,real-time quantitative PCR and western blot analysis.Exosomes derived from hAMSCs(hAMSCs-exo)and SCLCs were isolated by ultracentrifugation and validated by nanoparticle tracking analysis,WB analysis and electron microscopy.A prefab-ricated nerve graft was used to deliver hAMSCs-exo or SCLCs-exo in an injured sciatic nerve rat model.The effects of hAMSCs-exo or SCLCs-exo on rat peripheral nerve injury(PNI)regeneration were determined based on the recovery of neurological function and histomorphometric variation.The effects of hAMSCs-exo or SCLCs-exo on Schwann cells were also determined via cell prolifer-ation and migration assessment.Results:SCLCs significantly expressed the Schwann cell markers glial fibrillary acidic protein and S100.Compared to hAMSCs-exo,SCLCs-exo significantly enhanced motor function recov-ery,attenuated gastrocnemius muscle atrophy and facilitated axonal regrowth,myelin forma-tion and angiogenesis in the rat model.Furthermore,hAMSCs-exo and SCLCs-exo were effi-ciently absorbed by Schwann cells.However,compared to hAMSCs-exo,SCLCs-exo signifi-cantly promoted the proliferation and migration of Schwann cells.SCLCs-exo also significantly upregulated the expression of a glial cell-derived neurotrophic factor,myelin positive regulators(SRY-box transcription factor 10,early growth response protein 2 and organic cation/carnitine transporter 6)and myelin proteins(myelin basic protein and myelin protein zero)in Schwann cells.Conclusions:These findings suggest that SCLCs-exo can more efficiently promote PNI regeneration than hAMSCs-exo and are a potentially novel therapeutic approach for treating PNI.展开更多
Triclosan(TCS)is a ubiquitous antimicrobial used in daily consumer products.Previous reports have shown that TCS could induce hepatotoxicity,endocrine disruption,disturbance on immune function and impaired thyroid fun...Triclosan(TCS)is a ubiquitous antimicrobial used in daily consumer products.Previous reports have shown that TCS could induce hepatotoxicity,endocrine disruption,disturbance on immune function and impaired thyroid function.Kidney is critical in the elimination of toxins,while the effects of TCS on kidney have not yet been well-characterized.The aim of the present study was to investigate the effects of TCS exposure on kidney function and the possible underlying mechanisms in mice.Male C57BL/6 mice were orally exposed to TCS with the doses of 10 and 100 mg/(kg•day)for 13 weeks.TCS was dissolved in dimethyl sulfoxide(DMSO)and diluted by corn oil for exposure.Corn oil containing DMSO was used as vehicle control.Serum and kidney tissues were collected for study.Biomarkers associated with kidney function,oxidative stress,inflammation and fibrosis were assessed.Our results showed that TCS could cause renal injury as was revealed by increased levels of renal function markers including serum creatinine,urea nitrogen and uric acid,as well as increased oxidative stress,pro-inflammatory cytokines and fibroticmarkers in a dose dependent manner,whichweremore significantly in 100 mg/(kg•day)group.Mass spectrometry-based analysis of metabolites relatedwith lipid metabolism demonstrated the occurrence of lipid accumulation and defective fatty acid oxidation in 100 mg/(kg•day)TCS-exposed mouse kidney.These processes might lead to lipotoxicity and energy depletion,thus resulting in kidney fibrosis and functional decline.Taken together,the present study demonstrated that TCS could induce lipid accumulation and fatty acid metabolism disturbance in mouse kidney,whichmight contribute to renal function impairment.The present study further widens our insights into the adverse effects of TCS.展开更多
基金supported by the InnovationGroup Major Research Project of Guizhou Province Education Department(No.Qianjiaohe KY[2017]043)the Science and Technology Support Project of Guizhou Province(2020-5012)+3 种基金the PhD Fund of Scientific Research Foundation of the Affiliated Hospital of ZunyiMedical University(2020-03)the National Nature Science Foundation of China(81660325)the Collaborative Innovation Center of the Chinese Ministry of Education(2020-39)the Master Fund of Scientific Research Foundation of the Affiliated Hospital of Zunyi Medical University(2016-35).
文摘Background:Schwann cell-like cells(SCLCs),differentiated from mesenchymal stem cells,have shown promising outcomes in the treatment of peripheral nerve injuries in preclinical studies.However,certain clinical obstacles limit their application.Hence,the primary aim of this study was to investigate the role of exosomes derived from SCLCs(SCLCs-exo)in peripheral nerve regeneration.Methods:SCLCs were differentiated from human amniotic mesenchymal stem cells(hAMSCs)in vitro and validated by immunofluorescence,real-time quantitative PCR and western blot analysis.Exosomes derived from hAMSCs(hAMSCs-exo)and SCLCs were isolated by ultracentrifugation and validated by nanoparticle tracking analysis,WB analysis and electron microscopy.A prefab-ricated nerve graft was used to deliver hAMSCs-exo or SCLCs-exo in an injured sciatic nerve rat model.The effects of hAMSCs-exo or SCLCs-exo on rat peripheral nerve injury(PNI)regeneration were determined based on the recovery of neurological function and histomorphometric variation.The effects of hAMSCs-exo or SCLCs-exo on Schwann cells were also determined via cell prolifer-ation and migration assessment.Results:SCLCs significantly expressed the Schwann cell markers glial fibrillary acidic protein and S100.Compared to hAMSCs-exo,SCLCs-exo significantly enhanced motor function recov-ery,attenuated gastrocnemius muscle atrophy and facilitated axonal regrowth,myelin forma-tion and angiogenesis in the rat model.Furthermore,hAMSCs-exo and SCLCs-exo were effi-ciently absorbed by Schwann cells.However,compared to hAMSCs-exo,SCLCs-exo signifi-cantly promoted the proliferation and migration of Schwann cells.SCLCs-exo also significantly upregulated the expression of a glial cell-derived neurotrophic factor,myelin positive regulators(SRY-box transcription factor 10,early growth response protein 2 and organic cation/carnitine transporter 6)and myelin proteins(myelin basic protein and myelin protein zero)in Schwann cells.Conclusions:These findings suggest that SCLCs-exo can more efficiently promote PNI regeneration than hAMSCs-exo and are a potentially novel therapeutic approach for treating PNI.
基金supported by the National Natural Science Foundation of China (No. 21806135)the General Research Fund (No. 12301518) from Research Grants Council of Hong Kong
文摘Triclosan(TCS)is a ubiquitous antimicrobial used in daily consumer products.Previous reports have shown that TCS could induce hepatotoxicity,endocrine disruption,disturbance on immune function and impaired thyroid function.Kidney is critical in the elimination of toxins,while the effects of TCS on kidney have not yet been well-characterized.The aim of the present study was to investigate the effects of TCS exposure on kidney function and the possible underlying mechanisms in mice.Male C57BL/6 mice were orally exposed to TCS with the doses of 10 and 100 mg/(kg•day)for 13 weeks.TCS was dissolved in dimethyl sulfoxide(DMSO)and diluted by corn oil for exposure.Corn oil containing DMSO was used as vehicle control.Serum and kidney tissues were collected for study.Biomarkers associated with kidney function,oxidative stress,inflammation and fibrosis were assessed.Our results showed that TCS could cause renal injury as was revealed by increased levels of renal function markers including serum creatinine,urea nitrogen and uric acid,as well as increased oxidative stress,pro-inflammatory cytokines and fibroticmarkers in a dose dependent manner,whichweremore significantly in 100 mg/(kg•day)group.Mass spectrometry-based analysis of metabolites relatedwith lipid metabolism demonstrated the occurrence of lipid accumulation and defective fatty acid oxidation in 100 mg/(kg•day)TCS-exposed mouse kidney.These processes might lead to lipotoxicity and energy depletion,thus resulting in kidney fibrosis and functional decline.Taken together,the present study demonstrated that TCS could induce lipid accumulation and fatty acid metabolism disturbance in mouse kidney,whichmight contribute to renal function impairment.The present study further widens our insights into the adverse effects of TCS.
