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Engineering human islet organoids from iPSCs using an organ-on-chip platform

文献类型：期刊论文

作者Deng, Pengwei1,2; Tao, Tingting1,2; Wang, Yaqing1,2; Chen, Wenwen1,2; Li, Zhongyu2; Su, Wentao2; Guo, Yaqiong1,2; Qin, Jianhua1,2,3,4
刊名LAB ON A CHIP
出版日期2019-03-21
卷号19期号:6页码:948-958
ISSN号1473-0197
DOI10.1039/c8lc01298a
通讯作者Qin, Jianhua(jhqin@bdicp.ac.cn)
英文摘要Human pluripotent stem cell (hPSC)-derived islet cells provide promising resources for diabetes studies, cell replacement treatment and drug screening. Recently, hPSC-derived organoids have represented a new class of in vitro organ models for disease modeling and regenerative medicine. However, rebuilding biomimetic human islet organoids from hPSCs remains challenging. Here, we present a new strategy to engineer human islet organoids derived from human induced pluripotent stem cells (hiPSCs) using an organ-on-a-chip platform combined with stem cell developmental principles. The microsystem contains a multi-layer microfluidic device that allows controllable aggregation of embryoid bodies (EBs), in situ pancreatic differentiation and generation of heterogeneous islet organoids in parallel under perfused 3D culture in a single device. The generated islet organoids contain heterogeneous islet-specific a and beta-like cells that exhibit favorable growth and cell viability. They also show enhanced expression of pancreatic beta-cell specific genes and proteins (PDX1 and NKX6.1) and increased beta-cell hormone specific INS gene and C-peptide protein expressions under perfused 3D culture conditions compared to static cultures. In addition, the islet organoids exhibit more sensitive glucose-stimulated insulin secretion (GSIS) and higher Ca2+ flux, indicating the role of biomimetic mechanical flow in promoting endocrine cell differentiation and maturation of islet organoids. This islet-on-a-chip system is robust and amenable to real-time imaging and in situ tracking of islet organoid growth, which may provide a promising platform for organoid engineering, disease modeling, drug testing and regenerative medicine.
WOS关键词PANCREATIC BETA-CELLS ; STEM-CELLS ; A-CHIP ; GENERATION ; MODEL ; DIFFERENTIATION ; ORGANOGENESIS ; MATURATION
资助项目Strategic Priority Research Program of the Chinese Academy of Sciences[XDA16020900] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB29050301] ; National Key R&D Program of China[2017YFB0405400] ; Key Program of the Chinese Academy of Sciences[KFZD-SW-213] ; National Natural Science Foundation of China[91543121] ; National Natural Science Foundation of China[81573394] ; National Natural Science Foundation of China[81803492] ; China Postdoctoral Science Foundation[2018 M631836] ; Innovation Program of Science and Research from the DICP, CAS[DICP TMSR201601]
WOS研究方向Biochemistry & Molecular Biology ; Chemistry ; Science & Technology - Other Topics
语种英语
出版者ROYAL SOC CHEMISTRY
WOS记录号WOS:000462666200017
资助机构Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; National Key R&D Program of China ; National Key R&D Program of China ; Key Program of the Chinese Academy of Sciences ; Key Program of the Chinese Academy of Sciences ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; China Postdoctoral Science Foundation ; China Postdoctoral Science Foundation ; Innovation Program of Science and Research from the DICP, CAS ; Innovation Program of Science and Research from the DICP, CAS ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; National Key R&D Program of China ; National Key R&D Program of China ; Key Program of the Chinese Academy of Sciences ; Key Program of the Chinese Academy of Sciences ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; China Postdoctoral Science Foundation ; China Postdoctoral Science Foundation ; Innovation Program of Science and Research from the DICP, CAS ; Innovation Program of Science and Research from the DICP, CAS ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; National Key R&D Program of China ; National Key R&D Program of China ; Key Program of the Chinese Academy of Sciences ; Key Program of the Chinese Academy of Sciences ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; China Postdoctoral Science Foundation ; China Postdoctoral Science Foundation ; Innovation Program of Science and Research from the DICP, CAS ; Innovation Program of Science and Research from the DICP, CAS ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Strategic Priority Research Program of the Chinese Academy of Sciences ; National Key R&D Program of China ; National Key R&D Program of China ; Key Program of the Chinese Academy of Sciences ; Key Program of the Chinese Academy of Sciences ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; China Postdoctoral Science Foundation ; China Postdoctoral Science Foundation ; Innovation Program of Science and Research from the DICP, CAS ; Innovation Program of Science and Research from the DICP, CAS
源URL[http://cas-ir.dicp.ac.cn/handle/321008/165750]  
专题大连化学物理研究所_中国科学院大连化学物理研究所
通讯作者Qin, Jianhua
作者单位1.Univ Chinese Acad Sci, Beijing, Peoples R China
2.Chinese Acad Sci, Dalian Inst Chem Phys, Div Biotechnol, 457 Zhongshan Rd, Dalian 116023, Peoples R China
3.Chinese Acad Sci, Inst Stem Cell & Regenerat, Beijing, Peoples R China
4.Chinese Acad Sci, CAS Ctr Excellence Brain Sci & Intelligence Techn, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Deng, Pengwei,Tao, Tingting,Wang, Yaqing,et al. Engineering human islet organoids from iPSCs using an organ-on-chip platform[J]. LAB ON A CHIP,2019,19(6):948-958.
APA Deng, Pengwei.,Tao, Tingting.,Wang, Yaqing.,Chen, Wenwen.,Li, Zhongyu.,...&Qin, Jianhua.(2019).Engineering human islet organoids from iPSCs using an organ-on-chip platform.LAB ON A CHIP,19(6),948-958.
MLA Deng, Pengwei,et al."Engineering human islet organoids from iPSCs using an organ-on-chip platform".LAB ON A CHIP 19.6(2019):948-958.

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来源：大连化学物理研究所

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