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

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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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Late Triassic(Norian)Conodont Apparatuses Revealed by Conodont Clusters from Yunnan Province,Southwestern China

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Journal of Earth Science 2021年第3期32卷 709-724页

作者： Weiping zeng Mark A.Purnell Haishui Jiang muhui Zhang State Key Laboratory of Biogeology and Environmental Geology China University of GeosciencesWuhan 430078China School of Earth Sciences China University of GeosciencesWuhan 430074China Department of Geology University of LeicesterLeicester LEI 7RHUK

Almost all aspects of conodont research rely on a sound taxonomy based on comparative analysis.This is founded on hypotheses of homology which ultimately rest on knowledge of the location of elements in the apparatus.Natural assemblages—fossils that preserve the articulated remains of the conodont skeletal apparatus—provide our only direct evidence for element location,but very few are known from the Late Triassic.Here we describe fused clusters(natural assemblages)from the late Norian limestone beds of the Nanshuba Formation in Baoshan,Yunnan Province,southwestern China.Recurrent arrangements and juxtaposition of S and M elements in multiple clusters reveal the composition of the apparatus of Mockina and,probably,Parvigondolella.They indicate that these taxa had a standard 15 elements ozarkodinid apparatus,and provide new insights into the morphology of the elements occupying the P2,M and S locations of the apparatus.The apparatus comprised a single alate(hibbardelliform)S0 element,paired breviform digyrate(grodelliform)S1 and(enantiognathiform)S2 elements,paired bipennate(hindeodelliform)S3 and S4 elements,paired breviform digyrate(cypridodellifrom)M elements,paired,modified-angulate P2 elements(with reduced or lacking‘posterior’process)and segminiplanate(mockiniform and parvigondolelliform)P1 elements.Our results will allow testing of the hypothesis that Mockina,Parvigondolella and Misikella—critical taxa in Late Triassic biostratigraphy—are closely related and possessed morphologically similar elements in homologous locations.

关键词： conodont apparatus Mockina Parvigondolella Misikella Triassic

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