Injectable kartogenin and apocynin loaded micelle enhances the alleviation of intervertebral disc degeneration by adipose-derived stem cell  

作　　者：Chao Yu Dongdong Li Chenggui Wang Kaishun Xia Jingkai Wang Xiaopeng Zhou Liwei Ying Jiawei Shu Xianpeng Huang Haibin Xu Bin Han Qixin Chen Fangcai Li Jianbin Tang Chengzhen Liang Nigel Slater 

机构地区：[1]Department of Orthopedics Surgery,The Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou City,Zhejiang Province,PR China [2]Orthopedics Research Institute of Zhejiang University,Hangzhou City,Zhejiang Province,PR China [3]Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province,Hangzhou City,Zhejiang Province,PR China [4]Key Laboratory of Biomass Chemical Engineering of Ministry of Education,Center for Bionanoengineering,and College of Chemical and Biological Engineering,Zhejiang University,Hangzhou,Zhejiang,310027,China [5]Department of Chemical Engineering and Biotechnology,University of Cambridge,Cambridge,United Kingdom

出　　处：《Bioactive Materials》2021年第10期3568-3579,共12页生物活性材料（英文）

基　　金：This study was supported by grants from the Nature Science Foundation of Zhejiang Province(Y20H060063,LY19H060005,LQ18H060003,LR18E030002,LY18H060004);the Medical and Health Innovation Talent Support Program of Zhejiang Province(2020RC011);the National Natural Science Foundation of China(NO.82072465,NO.81772379,NO.81972096,NO.81902238,NO.21774109,NO.51973188,NO.51522304);the Health Foundation of Zhejiang Province(2018KY092,WKJ-ZJ-1903);the China Postdoctoral Science Foundation(2017M612011);the Zhejiang University Education Foundation Global Partnership Fund,a project supported by the Scientific Research Fund of Zhejiang Provincial Education Department(Y201941476 and Y201941491);Zhejiang Undergraduate Talent Project(grant no.2020R401212);the Scientific Research Fund of Zhejiang Provincial Education Department(Y201941476).

摘　　要：Cell transplantation has been proved the promising therapeutic effects on intervertebral disc degeneration(IVDD).However,the increased levels of reactive oxygen species(ROS)in the degenerated region will impede the efficiency of human adipose-derived stem cells(human ADSCs)transplantation therapy.It inhibits human ADSCs proliferation,and increases human ADSCs apoptosis.Herein,we firstly devised a novel amphiphilic copolymer PEG-PAPO,which could self-assemble into a nanosized micelle and load lipophilic kartogenin(KGN),as a single complex(PAKM).It was an injectable esterase-responsive micelle,and showed controlled release ability of KGN and apocynin(APO).Oxidative stimulation promoted the esterase activity in human ADSCs,which accelerate degradation of esterase-responsive micelle.Compared its monomer,the PAKM micelle possessed better bioactivities,which were attributed to their synergistic effect.It enhanced the viability,autophagic activation(P62,LC3 II),ECM-related transcription factor(SOX9),and ECM(Collagen II,Aggrecan)maintenance in human ADSCs.Furthermore,it is demonstrated that the injection of PAKM with human ADSCs yielded higher disc height and water content in rats.Therefore,PAKM micelles perform promoting cell survival and differentiation effects,and may be a potential therapeutic agent for IVDD.

关 键 词：Intervertebral disc degeneration Polymer-drug conjugates Mesenchymal stem cell Reactive oxygen species Stem cell therapy 

分 类 号：R681.53[医药卫生—骨科学]