Ischemic stroke is a major cause of mortality and disability worldwide,with limited treatment options available in clinical practice.The emergence of stem cell therapy has provided new hope to the field of stroke trea...Ischemic stroke is a major cause of mortality and disability worldwide,with limited treatment options available in clinical practice.The emergence of stem cell therapy has provided new hope to the field of stroke treatment via the restoration of brain neuron function.Exogenous neural stem cells are beneficial not only in cell replacement but also through the bystander effect.Neural stem cells regulate multiple physiological responses,including nerve repair,endogenous regeneration,immune function,and blood-brain barrier permeability,through the secretion of bioactive substances,including extracellular vesicles/exosomes.However,due to the complex microenvironment of ischemic cerebrovascular events and the low survival rate of neural stem cells following transplantation,limitations in the treatment effect remain unresolved.In this paper,we provide a detailed summary of the potential mechanisms of neural stem cell therapy for the treatment of ischemic stroke,review current neural stem cell therapeutic strategies and clinical trial results,and summarize the latest advancements in neural stem cell engineering to improve the survival rate of neural stem cells.We hope that this review could help provide insight into the therapeutic potential of neural stem cells and guide future scientific endeavors on neural stem cells.展开更多
Rationale:Chronic wounds associated with diabetes exact a heavy burden on individuals and society and do not have a specific treatment.Exosome therapy is an extension of stem cell therapy,and RNA interference(RNAi)-ba...Rationale:Chronic wounds associated with diabetes exact a heavy burden on individuals and society and do not have a specific treatment.Exosome therapy is an extension of stem cell therapy,and RNA interference(RNAi)-based therapy is a type of advanced precision therapy.Based on the discovery of chronic wound-related genes in diabetes,we combined exosome therapy and RNAi therapy through an engineering approach for the treatment of diabetic chronic wounds.Methods:We combined exosome therapy and RNAi therapy to establish a precision therapy for diabetes-associated wounds via an engineered exosome approach.Results:First,chronic diabetic wounds express low levels of miR-31-5p compared with nondiabetic wounds,and an miR-31-5p mimic was shown to be effective in promoting the proliferation and migration of three wound-related cell types in vitro.Second,bioinformatics analysis,luciferase reporter assays and western blotting suggested that miR-31-5p promoted angiogenesis,fibrogenesis and reepithelization by inhibiting factor-inhibiting HIF-1(HIF1AN,also named FIH)and epithelial membrane protein-1(EMP-1).Third,engineered miR-31 exosomes were generated as a miR-31-5p RNAi therapeutic agent.In vivo,the engineered miR-31 exosomes promoted diabetic wound healing by enhancing angiogenesis,fibrogenesis and reepithelization.Conclusion:Engineered miR-31 exosomes are an ideal disease pathophysiology-initiated RNAi therapeutic agent for diabetic wounds.展开更多
基金supported by the National Natural Science Foundation of China,No.81971105(to ZNG)the Science and Technology Department of Jilin Province,No.YDZJ202201ZYTS677(to ZNG)+3 种基金Talent Reserve Program of the First Hospital of Jilin University,No.JDYYCB-2023002(to ZNG)the Norman Bethune Health Science Center of Jilin University,No.2022JBGS03(to YY)Science and Technology Department of Jilin Province,Nos.YDZJ202302CXJD061,20220303002SF(to YY)Jilin Provincial Key Laboratory,No.YDZJ202302CXJD017(to YY).
文摘Ischemic stroke is a major cause of mortality and disability worldwide,with limited treatment options available in clinical practice.The emergence of stem cell therapy has provided new hope to the field of stroke treatment via the restoration of brain neuron function.Exogenous neural stem cells are beneficial not only in cell replacement but also through the bystander effect.Neural stem cells regulate multiple physiological responses,including nerve repair,endogenous regeneration,immune function,and blood-brain barrier permeability,through the secretion of bioactive substances,including extracellular vesicles/exosomes.However,due to the complex microenvironment of ischemic cerebrovascular events and the low survival rate of neural stem cells following transplantation,limitations in the treatment effect remain unresolved.In this paper,we provide a detailed summary of the potential mechanisms of neural stem cell therapy for the treatment of ischemic stroke,review current neural stem cell therapeutic strategies and clinical trial results,and summarize the latest advancements in neural stem cell engineering to improve the survival rate of neural stem cells.We hope that this review could help provide insight into the therapeutic potential of neural stem cells and guide future scientific endeavors on neural stem cells.
基金The authors acknowledge the support of the National Natural Science Foundation of China(81572178,81270397,81702317,81871752 and 81770802)the National Key R&D Program of China(2017YFC1309601 to Fang Liu)+1 种基金Shanghai Municipal Commission of Health and Family Planning under the fund(20124356)a Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant(20152232).
文摘Rationale:Chronic wounds associated with diabetes exact a heavy burden on individuals and society and do not have a specific treatment.Exosome therapy is an extension of stem cell therapy,and RNA interference(RNAi)-based therapy is a type of advanced precision therapy.Based on the discovery of chronic wound-related genes in diabetes,we combined exosome therapy and RNAi therapy through an engineering approach for the treatment of diabetic chronic wounds.Methods:We combined exosome therapy and RNAi therapy to establish a precision therapy for diabetes-associated wounds via an engineered exosome approach.Results:First,chronic diabetic wounds express low levels of miR-31-5p compared with nondiabetic wounds,and an miR-31-5p mimic was shown to be effective in promoting the proliferation and migration of three wound-related cell types in vitro.Second,bioinformatics analysis,luciferase reporter assays and western blotting suggested that miR-31-5p promoted angiogenesis,fibrogenesis and reepithelization by inhibiting factor-inhibiting HIF-1(HIF1AN,also named FIH)and epithelial membrane protein-1(EMP-1).Third,engineered miR-31 exosomes were generated as a miR-31-5p RNAi therapeutic agent.In vivo,the engineered miR-31 exosomes promoted diabetic wound healing by enhancing angiogenesis,fibrogenesis and reepithelization.Conclusion:Engineered miR-31 exosomes are an ideal disease pathophysiology-initiated RNAi therapeutic agent for diabetic wounds.
