Mesenchymal stem cells(MSCs)therapy shows the potential benefits to relieve clinical symptoms of osteoarthritis(OA),but it is uncertain if it can repair articular cartilage lesions-the main pathology of OA.Here,we pre...Mesenchymal stem cells(MSCs)therapy shows the potential benefits to relieve clinical symptoms of osteoarthritis(OA),but it is uncertain if it can repair articular cartilage lesions-the main pathology of OA.Here,we prepared biomimetic cupper sulfide@phosphatidylcholine(CuS@PC)nanoparticles(NPs)loaded with plasmid DNA(pDNA)encoding transforming growth factor-beta 1(TGF-β1)to engineer MSCs for enhanced OA therapy via cartilage regeneration.We found that the NPs not only promoted cell proliferation and migration,but also presented a higher pDNA transfection efficiency relative to commercial transfection reagent lipofectamine 3000.The resultant CuS/TGF-β1@PC NP-engineered MSCs(termed CTP-MSCs)were better than pure MSCs in terms of chondrogenic gene expression,glycosaminoglycan deposition and type II collagen formation,favoring cartilage repair.Further,CTP-MSCs inhibited extracellular matrix degradation in interleukin-1β-induced chondrocytes.Consequently,intraarticular administration of CTP-MSCs significantly enhanced the repair of damaged cartilage,whereas pure MSCs exhibited very limited effects on cartilage regeneration in destabilization of the medial meniscus(DMM)surgical instability mice.Hence,this work provides a new strategy to overcome the limitation of current stem cell therapy in OA treatment through developing more effective nanoengineered MSCs.展开更多
Randomized controlled trials(RCTs)provide optimal evidence of the effectiveness and safety of a new drug,a new medical device,or a new therapeutic strategy with the necessary scientific design[1].Traditional electroni...Randomized controlled trials(RCTs)provide optimal evidence of the effectiveness and safety of a new drug,a new medical device,or a new therapeutic strategy with the necessary scientific design[1].Traditional electronic data collection(EDC)systems for clinical trials primarily focus on data entry,validation,and compliance monitoring.However,their reliance on centralized architectures introduces vulnerabilities in data security and integrity。展开更多
Introduction:Osteoarthritis(OA)is the most common joint disorder in the world but there are no approved therapies to slow disease progression.Historically,OA has been considered a wear and tear joint disease and effor...Introduction:Osteoarthritis(OA)is the most common joint disorder in the world but there are no approved therapies to slow disease progression.Historically,OA has been considered a wear and tear joint disease and efforts to identify and develop disease modifying therapies have primarily focused on inhibiting cartilage degradation directly.However,increasing studies have suggested that inflammation is a key player of joint pathology in some OA patients and also a link between obesity and OA.Therefore,targeting inflammation in these patients could be a promising therapeutic strategy.Areas Covered:In this review,we collate the latest evidence on the relationship between inflammation and OA which allows to propose the inflammatory phenotype of OA,and summarize major results of some emerging therapies targeting this phenotype in clinical trials which could implicate future directions for OA treatment.Expert Opinion:The authors believe early diagnosis,phenotyping OA patients and precise therapies would expedite the development of DMOADs targeting OA inflammatory phenotype.In the future,well-designed clinical trials including appropriate subgroups or phenotypes of patients according to underlying causes and mechanisms of OA are expected for investigational therapies.展开更多
基金supported by National Natural Science Foundation of China(81902198,81974342,82172391)Guangdong Basic and Applied Basic Research Foundation(2020A1515010398)+2 种基金China National Postdoctoral Program for Innovative Talents(BX20190150)China Postdoctoral Science Foundation(2019M662980)President Foundation of Zhujiang Hospital,Southern Medical University(yzjj2018rc09).
文摘Mesenchymal stem cells(MSCs)therapy shows the potential benefits to relieve clinical symptoms of osteoarthritis(OA),but it is uncertain if it can repair articular cartilage lesions-the main pathology of OA.Here,we prepared biomimetic cupper sulfide@phosphatidylcholine(CuS@PC)nanoparticles(NPs)loaded with plasmid DNA(pDNA)encoding transforming growth factor-beta 1(TGF-β1)to engineer MSCs for enhanced OA therapy via cartilage regeneration.We found that the NPs not only promoted cell proliferation and migration,but also presented a higher pDNA transfection efficiency relative to commercial transfection reagent lipofectamine 3000.The resultant CuS/TGF-β1@PC NP-engineered MSCs(termed CTP-MSCs)were better than pure MSCs in terms of chondrogenic gene expression,glycosaminoglycan deposition and type II collagen formation,favoring cartilage repair.Further,CTP-MSCs inhibited extracellular matrix degradation in interleukin-1β-induced chondrocytes.Consequently,intraarticular administration of CTP-MSCs significantly enhanced the repair of damaged cartilage,whereas pure MSCs exhibited very limited effects on cartilage regeneration in destabilization of the medial meniscus(DMM)surgical instability mice.Hence,this work provides a new strategy to overcome the limitation of current stem cell therapy in OA treatment through developing more effective nanoengineered MSCs.
基金supported by the National Natural Science Foundation of China(92368205 and 82301265)the Guangdong Provincial Natural Science Foundation for Progressive Young Scholars(2023A1515030170)+3 种基金the Science and Technology Planning Projects of Guangdong Province(2018B010109008)the Science and Technology Planning Project of the Guangzhou Municipal Health Commission(2024A031004)the Basic Scientific Research Projects of Sun Yat-sen University(23ykcxqt002)the China Postdoctoral Science Foundation(2023M734047).
文摘Randomized controlled trials(RCTs)provide optimal evidence of the effectiveness and safety of a new drug,a new medical device,or a new therapeutic strategy with the necessary scientific design[1].Traditional electronic data collection(EDC)systems for clinical trials primarily focus on data entry,validation,and compliance monitoring.However,their reliance on centralized architectures introduces vulnerabilities in data security and integrity。
文摘Introduction:Osteoarthritis(OA)is the most common joint disorder in the world but there are no approved therapies to slow disease progression.Historically,OA has been considered a wear and tear joint disease and efforts to identify and develop disease modifying therapies have primarily focused on inhibiting cartilage degradation directly.However,increasing studies have suggested that inflammation is a key player of joint pathology in some OA patients and also a link between obesity and OA.Therefore,targeting inflammation in these patients could be a promising therapeutic strategy.Areas Covered:In this review,we collate the latest evidence on the relationship between inflammation and OA which allows to propose the inflammatory phenotype of OA,and summarize major results of some emerging therapies targeting this phenotype in clinical trials which could implicate future directions for OA treatment.Expert Opinion:The authors believe early diagnosis,phenotyping OA patients and precise therapies would expedite the development of DMOADs targeting OA inflammatory phenotype.In the future,well-designed clinical trials including appropriate subgroups or phenotypes of patients according to underlying causes and mechanisms of OA are expected for investigational therapies.
