Tumor necrosis factor-αinhibition restores matrix formation by human adipose-derived stem cells in the late stage of chondrogenic differentiation  

作　　者：Jiang-Tao Wan Xian-Shuai Qiu Zhuo-Hang Fu Yong-Can Huang Shao-Xiong Min 

机构地区：[1]Department of Spine Surgery,Peking University Shenzhen Hospital,Shenzhen 518036,Guangdong Province,China [2]Institute of Orthopedics,Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center,Shenzhen 518036,Guangdong Province,China [3]Department of Spine Surgery,Zhujiang Hospital,Southern Medical University,Guangzhou 510280,Guangdong Province,China

出　　处：《World Journal of Stem Cells》2022年第11期798-814,共17页世界干细胞杂志（英文版）（电子版）

基　　金：Thanks to Peking University Hong Kong University of Science and Technology Medical Center for providing the research instruments and workplace.

摘　　要：BACKGROUND Cartilage tissue engineering is a promising strategy for treating cartilage damage.Matrix formation by adipose-derived stem cells(ADSCs),which are one type of seed cell used for cartilage tissue engineering,decreases in the late stage of induced chondrogenic differentiation in vitro,which seriously limits research on ADSCs and their application.AIM To improve the chondrogenic differentiation efficiency of ADSCs in vitro,and optimize the existing chondrogenic induction protocol.METHODS Tumor necrosis factor-alpha(TNF-α)inhibitor was added to chondrogenic culture medium,and then Western blotting,enzyme linked immunosorbent assay,immunofluorescence and toluidine blue staining were used to detect the cartilage matrix secretion and the expression of key proteins of nuclear factor kappa-B(NF-κB)signaling pathway.RESULTS In this study,we found that the levels of TNF-αand matrix metalloproteinase 3 were increased during the chondrogenic differentiation of ADSCs.TNF-αthen bound to its receptor and activated the NF-κB pathway,leading to a decrease in cartilage matrix synthesis and secretion.Blocking TNF-αwith its inhibitors etanercept(1μg/mL)or infliximab(10μg/mL)significantly restored matrix formation.CONCLUSION Therefore,this study developed a combination of ADSC therapy and targeted anti-inflammatory drugs to optimize the chondrogenesis of ADSCs,and this approach could be very beneficial for translating ADSC-based approaches to treat cartilage damage.

关 键 词：Adipose-derived mesenchymal stem cells Human adipose-derived mesenchymal stem cells Chondrogenic differentiation Tumor necrosis factor-alpha ETANERCEPT INFLIXIMAB Nuclear factor kappa-B 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]