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

引用

Bioactive Materials 2023年第1期19卷 444-457页

作者： Yu Cai Cuixi Wu Qianhua Ou Muhui Zeng Song Xue Jieli Chen Yao Lu Changhai Ding Clinical Research Center Zhujiang HospitalSouthern Medical UniversityGuangzhouGuangdong510282China Orthopedic Center Zhujiang HospitalSouthern Medical UniversityGuangzhouGuangdong510282China Guangdong Key Lab of Orthopedic Technology and Implant GuangzhouGuangdong510010China Department of Rheumatology and Immunology Arthritis Research InstituteThe First Affiliated Hospital of Anhui Medical UniversityHefeiAnhui230032China Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases Academy of OrthopedicsSouthern Medical UniversityGuangzhouGuangdong510630China Menzies Institute for Medical Research University of TasmaniaHobartTasmania7000Australia

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.

关键词： Osteoarthritis Stem cell therapy Cartilage regeneration Cupper sulfide nanoparticles Gene delivery

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