Mechanical stretching boosts expansion and regeneration of intestinal organoids through fueling stem cell self-renewal  

作　　者：Fanlu Meng Congcong Shen Li Yang Chao Ni Jianyong Huang Kaijun Lin Zanxia Cao Shicai Xu Wanling Cui Xiaoxin Wang Bailing Zhou Chunyang Xiong Jihua Wang Bing Zhao 

机构地区：[1]Shandong Key Laboratory of Biophysics,Institute of Biophysics,Dezhou University,Dezhou 253023,China [2]Department of Mechanics and Engineering Science,College of Engineering,Peking University,Beijing 100871,China [3]State Key Laboratory of Genetic Engineering,School of Life Sciences,Zhongshan Hospital,Fudan University,Shanghai 200438,China [4]Beijing Innovation Center for Engineering Science and Advanced Technology,College of Engineering,Peking University,Beijing 100871,China [5]Wenzhou Institute,University of Chinese Academy of Sciences,Oujiang Laboratory,Wenzhou 325000,Zhejiang,China

出　　处：《Cell Regeneration》2022年第1期399-412,共14页细胞再生（英文）

基　　金：This work was supported from the National Key Research and Development Program of China(2018YFA0109400);the National Natural Science Foundation of China(32022022,11972002,11972001,62071085);Beijing Natural Science Foundation(Z200017);Natural Science Foundation of Shandong Province(ZR2019PC026);the Open Research Fund of Shandong Key Laboratory of Biophysics of Dezhou College(SD2018BP005).

摘　　要：Intestinal organoids,derived from intestinal stem cell self-organization,recapitulate the tissue structures and behav-iors of the intestinal epithelium,which hold great potential for the study of developmental biology,disease modeling,and regenerative medicine.The intestinal epithelium is exposed to dynamic mechanical forces which exert profound effects on gut development.However,the conventional intestinal organoid culture system neglects the key role of mechanical microenvironments but relies solely on biological factors.Here,we show that adding cyclic stretch to intestinal organoid cultures remarkably up-regulates the signature gene expression and proliferation of intestinal stem cells.Furthermore,mechanical stretching stimulates the expansion of SOX9+progenitors by activating the Wnt/β-Catenin signaling.These data demonstrate that the incorporation of mechanical stretch boosts the stemness of intestinal stem cells,thus benefiting organoid growth.Our findings have provided a way to optimize an organoid generation system through understanding cross-talk between biological and mechanical factors,paving the way for the application of mechanical forces in organoid-based models.

关 键 词：Mechanical stretching Intestinal organoid Lgr5+stem cell REGENERATION Wnt/β-catenin signaling 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]