Microfluidic intestinal organoid-on-a-chip uncovers therapeutic targets by recapitulating oxygen dynamics of intestinal IR injury

查看全文 作　　者：Jinjian [1]Huang;Ziyan [2]Xu;Jiao [3]Jiao;Zongan [4]Li;Sicheng [2]Li;Ye [1]Liu;Ze [2]Li;Guiwen [1]Qu;Jie [5]Wu;Yun [5]Zhao;Kang [2]Chen;Jieshou [1]Li;Yichang [6]Pan;Xiuwen [1,2]Wu;Jianan [1,2]Ren

机构地区：[1]Research Institute of General Surgery,Jinling Hospital,School of Medicine,Southeast University,Nanjing,210009,China;[2]School of Medicine,Nanjing University,Nanjing,210093,China;[3]Department of Rehabilitation,The First Affiliated Hospital of Nanjing Medical University,Nanjing,210029,China;[4]Jiangsu Key Laboratory of 3D Printing Equipment and Manufacturing,NARI School of Electrical and Automation Engineering,Nanjing Normal University,Nanjing,210042,China;[5]General Clinical Research Center,Nanjing Benq Hospital,Nanjing Medical University,Nanjing,210019,China;[6]State Key Laboratory of Materials-Oriented Chemical Engineering,College of Chemical Engineering,Nanjing Tech University,Nanjing,211816,China

出　　处：《Bioactive Materials》索引2023年第12期,共14页

基　　金：the National Natural Science Foundation of China(82270595,82272237,82072223,32171402);the China Postdoctoral Science Foundation(BX20220393,2022M723891);the General Program of Medical Research from the Jiangsu Commission of Health(M2020052);the Jiangsu Key Research and Development Plan(BE2021727);Jiangsu Provincial Medical Innovation Center(CXZX202217). 摘　　要：Increasing evidence demonstrates that mammals have different reactions to hypoxia with varied oxygen dynamic patterns.It takes~24 h for tri-gas incubator to achieve steady cell hypoxia,which fails to recapitulate ultrafast oxygen dynamics of intestinal ischemia/reperfusion(IR)injury.Inspired from the structure of native intestinal villi,we engineered an intestinal organoid chip embedded with engineered artificial microvessels based on coaxial microfluidic technology by using pH-responsive ZIF-8/sodium alginate scaffold.The chip was featured on:(i)eight times the oxygen exchange efficiency compared with the conventional device,tri-gas incubator,(ii)implantation of intestinal organoid reproducing all types of intestinal epithelial cells,and(iii)bio-responsiveness to hypoxia and reoxygenation(HR)by presenting metabolism disorder,inflammatory reaction,and cell apoptosis.Strikingly,it was found for the first time that Olfactomedin 4(Olfm4)was the most significantly downregulated gene under a rapid HR condition by sequencing the RNA from the organoids.Mechanistically,OLFM4 played protective functions on HR-induced cell inflammation and tissue damage by inhibiting the NF-kappa B signaling activation,thus it could be used as a therapeutic target.Altogether,this study overcomes the issue of mismatched oxygen dynamics between in vitro and in vivo,and sets an example of next-generation multisysteminteractive organoid chip for finding precise therapeutic targets of IR injury. 关键词：Ionic barrier of ZIF-8 MICROFLUIDICS Organoid-on-a-chip Oxygen dynamics Olfm4

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Microfluidic intestinal organoid-on-a-chip uncovers therapeutic targets by recapitulating oxygen dynamics of intestinal IR injury

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