Enhanced osteoarthritis therapy by nanoengineered mesenchymal stem cells using biomimetic CuS nanoparticles loaded with plasmid DNA encoding TGF-β1

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.

Inflammatory phenotype of osteoarthritis and its potential therapies

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.