Tissue-engineered mesenchymal stem cell constructs alleviate tendinopathy by suppressing vascularization  

作　　者：Dijun Li Jingwei Jiu Haifeng Liu Xiaojun Yan Xiaoke Li Lei Yan Jing Zhang Zijuan Fan Songyan Li Guangyuan Du Jiao Jiao Li Yanan Du Wei Liu Bin Wang 

机构地区：[1]Department of Orthopaedic Surgery,The First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou,310006,China [2]Department of Orthopedics,The Second Hospital of Shanxi Medical University,Taiyuan,030001,China [3]Department of Orthopedics,Affiliated Renhe Hospital of China Three Gorges University,Yichang,China [4]Department of Biomedical Engineering,School of Medicine,Tsinghua-Peking Center for Life Sciences,Tsinghua University,Beijing,100084,China [5]Beijing CytoNiche Biotechnology Co.Ltd,Beijing,10081,China [6]Department of Emergency Surgery,The Affiliated Hospital of Guizhou Medical University,Guiyang,Guizhou,550001,China [7]Department of Health Statistics,School of Public Health,Shanxi Medical University,Taiyuan,030001,China [8]School of Biomedical Engineering,Faculty of Engineering and IT,University of Technology Sydney,Sydney,NSW,2007,Australia

出　　处：《Bioactive Materials》2024年第6期474-489,共16页生物活性材料（英文）

基　　金：supported by the National Natural Science Foundation of China(81802204)a;by Zhejiang University School of Medicine,The First Affiliated Hospital’s Foundation(G2022010-18);Alibaba Cloud,Zhejiang Medical and Health Science and Technology Project(2023RC010);Natural Science Foundation of Zhejiang Province(LTGY23H060007);National Health and Medical Research Council(NHMRC,Australia;GNT1120249).

摘　　要：Tendinopathy leads to low-grade tissue inflammation and chronic damage,which progresses due to pathological imbalance in angiogenesis.Reducing early path-ological vascularization may be a new approach in helping to regenerate tendon tissue.Conventional stem cell therapy and tissue engineering scaffolds have not been highly effective at treating tendinopathy.In this study,tissue engineered stem cells(TSCs)generated using human umbilical cord mesenchymal stem cells(hUC-MSCs)were combined with microcarrier scaffolds to limit excessive vascularization in tendinopathy.By preventing VEGF receptor activation through their paracrine function,TSCs reduced in vitro angiogenesis and the proliferation of vascular endothelial cells.TSCs also decreased the inflammatory expression of tenocytes while promoting their anabolic and tenogenic characteristics.Furthermore,local injection of TSCs into rats with collagenase-induced tendinopathy substantially reduced early inflammation and vascularization.Mechanistically,transcriptome sequencing revealed that TSCs could reduce the progression of pathological angiogenesis in tendon tissue,attributed to Rap1-mediated vascular inhibition.TSCs may serve as a novel and practical approach for suppressing tendon vascularization,and provide a promising therapeutic agent for early-stage clinical tendinopathy.

关 键 词：inflammation injection VASCULAR 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]