Integrin beta 3-overexpressing mesenchymal stromal cells display enhanced homing and can reduce atherosclerotic plaque  

作　　者：Hai-Juan Hu Xue-Ru Xiao Tong Li De-Min Liu Xue Geng Mei Han Wei Cui 

机构地区：[1]First Division,Department of Cardiology,The Second Hospital of Hebei Medical University and Institute of Cardiocerebrovascular Disease of Hebei Province,Shijiazhuang 050000,Hebei Province,China [2]Department of Obstetrics,Shijiazhuang People's Hospital,Shijiazhuang 050030,Hebei Province,China [3]Key Laboratory of Medical Biotechnology of Hebei Province,Department of Biochemistry and Molecular Biology,College of Basic Medicine,Cardiovascular Medical Science Center,Hebei Medical University,Shijiazhuang 050017,Hebei Province,China

出　　处：《World Journal of Stem Cells》2023年第9期931-946,共16页世界干细胞杂志（英文版）（电子版）

基　　金：National Natural Science Foundation of China,No.82100301;Key Science and Technology Research Program of Hebei Provincial Department of Health,No,20221014.

摘　　要：BACKGROUND Umbilical cord(UC)mesenchymal stem cell(MSC)transplantation is a potential therapeutic intervention for atherosclerotic vascular disease.Integrin beta 3(ITGB3)promotes cell migration in several cell types.However,whether ITGBmodified MSCs can migrate to plaque sites in vivo and play an anti-atherosclerotic role remains unclear.AIM To investigate whether ITGB3-overexpressing MSCs(MSCs^(ITGB3))would exhibit improved homing efficacy in atherosclerosis.METHODS UC MSCs were isolated and expanded.Lentiviral vectors encoding ITGB3 or green fluorescent protein(GFP)as control were transfected into MSCs.Sixty male apolipoprotein E-/-mice were acquired from Beijing Vital River Lab Animal Technology Co.,Ltd and fed with a high-fat diet(HFD)for 12 wk to induce the formation of atherosclerotic lesions.These HFD-fed mice were randomly separated into three clusters.GFP-labeled MSCs(MSCs^(GFP))or MSCs^(ITGB3)were transplanted into the mice intravenously via the tail vein.Immunofluorescence staining,Oil red O staining,histological analyses,western blotting,enzymelinked immunosorbent assay,and quantitative real-time polymerase chain reaction were used for the analyses.RESULTS ITGB3 modified MSCs successfully differentiated into the“osteocyte”and“adipocyte”phenotypes and were characterized by positive expression(>91.3%)of CD29,CD73,and CD105 and negative expression(<1.35%)of CD34 and Human Leukocyte Antigen-DR.In a transwell assay,MSCs^(ITGB3)showed significantly faster migration than MSCsGFP.ITGB3 overexpression had no effects on MSC viability,differentiation,and secretion.Immunofluorescence staining revealed that ITGB3 overexpression substantially enhanced the homing of MSCs to plaque sites.Oil red O staining and histological analyses further confirmed the therapeutic effects of MSCs^(ITGB3),significantly reducing the plaque area.Enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction revealed that MSC^(ITGB3)transplantation considerably decreased the inflammatory response in patho

关 键 词：ATHEROSCLEROSIS INFLAMMATION Integrin beta 3 Mesenchymal stem cells Arg-Gly-Asp structure Umbilical cord 

分 类 号：R681.55[医药卫生—骨科学]