Brain tissues that are severely damaged by traumatic brain injury(TBI)is hardly regenerated,which leads to a cavity or a repair with glial scarring.Stem-cell therapy is one viable option to treat TBI-caused brain tiss...Brain tissues that are severely damaged by traumatic brain injury(TBI)is hardly regenerated,which leads to a cavity or a repair with glial scarring.Stem-cell therapy is one viable option to treat TBI-caused brain tissue damage,whose use is,whereas,limited by the low survival rate and differentiation efficiency of stem cells.To approach this problem,we developed an injectable hydrogel using imidazole groups-modified gelatin methacrylate(GelMA-imid).In addition,polydopamine(PDA)nanoparticles were used as carrier for stromal-cell derived factor-1(SDF-1α).GelMA-imid hydrogel loaded with PDA@SDF-1αnanoparticles and human amniotic mesenchymal stromal cells(hAMSCs)were injected into the damaged area in an in-vivo cryogenic injury model in rats.The hydrogel had low module and its average pore size was 204.61±41.41 nm,which were suitable for the migration,proliferation and differentiation of stem cells.In-vitro cell scratch and differentiation assays showed that the imidazole groups and SDF-1αcould promote the migration of hAMSCs to injury site and their differentiation into nerve cells.The highest amount of nissl body was detected in the group of GelMA-imid/SDF-1α/hAMSCs hydrogel in the in-vivo model.Additionally,histological analysis showed that GelMA-imid/SDF-1α/hAMSCs hydrogel could facilitate the regeneration of regenerate endogenous nerve cells.In summary,the GelMA-imid/SDF-1α/hAMSCs hydrogel promoted homing and differentiation of hAMSCs into nerve cells,and showed great application potential for the physiological recovery of TBI.展开更多
Background:The immunomodulatory effects of mesenchymal stem cells(MSCs)and their exosomes have been receiving increasing attention.This study investigated the immunoregulatory effects of human amniotic mesenchymal ste...Background:The immunomodulatory effects of mesenchymal stem cells(MSCs)and their exosomes have been receiving increasing attention.This study investigated the immunoregulatory effects of human amniotic mesenchymal stem cells(hAMSCs)and their exosomes on phytohemagglutinin(PHA)-induced peripheral blood mononuclear cells(PBMCs).Methods:The hAMSCs used in the experiment were identified by light microscopy and flow cytometry,and the differentiation ability of the cells was determined by Oil Red O and Alizarin Red staining.The expressions of transforming growth factor(TGF)-β,indoleamine 2,3-dioxygenase(IDO),cyclooxygenase-2(COX-2),hepatocyte growth factor(HGF),and interleukin(IL)-6 were detected by quantitative real-time polymerase chain reaction and western blotting.PBMCs,hAMSCs,and their exosomes were collected for in vitro group culture.Then the immunoregulatory ability of hAMSCs and their exosomes were analyzed by flow cytometry and Enzymelinked immunosorbent assay.Results:The hAMSCs and exosomes were successfully extracted from the human amniotic membrane.TGF-β,IDO,COX-2,HGF,and IL-6 were significantly expressed in hAMSCs.In vitro co-culture showed that hAMSCs promoted the proliferation of Th2 cells in PHA-induced PBMCs,while hAMSCs and exosomes inhibited the secretion of TNF-αin PHA-induced PBMCs,and promoted the secretion of IL-4 and IL-10,and hAMSCs had more significant effects than exosomes.Conclusions:hAMSCs or exosomes could exert immunoregulatory effects on PHA-induced PBMCs by affecting Th2 cell proliferation and cytokine secretion.展开更多
基金financially supported by the Science and Technology Project of Guangdong Province(No.2015A020212021)Medical Health Science and Technology Project of Zhejiang Provincial Health Commission(No.2020KY625)+4 种基金Zhejiang Provincial Department of Education(No.Y201636248)Natural Science Foundation of Zhejiang Province(No.LQY17H140023)Science Technology Department of Zhejiang Province(No.2017C33168)Zhejiang Provincial Basic Public Welfare Research Project(No.GJ19H140001)China's National Key R&D Programs(No.2018YFB0407204).
文摘Brain tissues that are severely damaged by traumatic brain injury(TBI)is hardly regenerated,which leads to a cavity or a repair with glial scarring.Stem-cell therapy is one viable option to treat TBI-caused brain tissue damage,whose use is,whereas,limited by the low survival rate and differentiation efficiency of stem cells.To approach this problem,we developed an injectable hydrogel using imidazole groups-modified gelatin methacrylate(GelMA-imid).In addition,polydopamine(PDA)nanoparticles were used as carrier for stromal-cell derived factor-1(SDF-1α).GelMA-imid hydrogel loaded with PDA@SDF-1αnanoparticles and human amniotic mesenchymal stromal cells(hAMSCs)were injected into the damaged area in an in-vivo cryogenic injury model in rats.The hydrogel had low module and its average pore size was 204.61±41.41 nm,which were suitable for the migration,proliferation and differentiation of stem cells.In-vitro cell scratch and differentiation assays showed that the imidazole groups and SDF-1αcould promote the migration of hAMSCs to injury site and their differentiation into nerve cells.The highest amount of nissl body was detected in the group of GelMA-imid/SDF-1α/hAMSCs hydrogel in the in-vivo model.Additionally,histological analysis showed that GelMA-imid/SDF-1α/hAMSCs hydrogel could facilitate the regeneration of regenerate endogenous nerve cells.In summary,the GelMA-imid/SDF-1α/hAMSCs hydrogel promoted homing and differentiation of hAMSCs into nerve cells,and showed great application potential for the physiological recovery of TBI.
基金Research Program of Health Committee of Hunan Province(202106010870)to Xin Tian.
文摘Background:The immunomodulatory effects of mesenchymal stem cells(MSCs)and their exosomes have been receiving increasing attention.This study investigated the immunoregulatory effects of human amniotic mesenchymal stem cells(hAMSCs)and their exosomes on phytohemagglutinin(PHA)-induced peripheral blood mononuclear cells(PBMCs).Methods:The hAMSCs used in the experiment were identified by light microscopy and flow cytometry,and the differentiation ability of the cells was determined by Oil Red O and Alizarin Red staining.The expressions of transforming growth factor(TGF)-β,indoleamine 2,3-dioxygenase(IDO),cyclooxygenase-2(COX-2),hepatocyte growth factor(HGF),and interleukin(IL)-6 were detected by quantitative real-time polymerase chain reaction and western blotting.PBMCs,hAMSCs,and their exosomes were collected for in vitro group culture.Then the immunoregulatory ability of hAMSCs and their exosomes were analyzed by flow cytometry and Enzymelinked immunosorbent assay.Results:The hAMSCs and exosomes were successfully extracted from the human amniotic membrane.TGF-β,IDO,COX-2,HGF,and IL-6 were significantly expressed in hAMSCs.In vitro co-culture showed that hAMSCs promoted the proliferation of Th2 cells in PHA-induced PBMCs,while hAMSCs and exosomes inhibited the secretion of TNF-αin PHA-induced PBMCs,and promoted the secretion of IL-4 and IL-10,and hAMSCs had more significant effects than exosomes.Conclusions:hAMSCs or exosomes could exert immunoregulatory effects on PHA-induced PBMCs by affecting Th2 cell proliferation and cytokine secretion.
