PMID- 34951149
OWN - NLM
STAT- MEDLINE
DCOM- 20220407
LR  - 20220407
IS  - 2198-3844 (Electronic)
IS  - 2198-3844 (Linking)
VI  - 9
IP  - 5
DP  - 2022 Feb
TI  - Microengineered Multi-Organoid System from hiPSCs to Recapitulate Human 
      Liver-Islet Axis in Normal and Type 2 Diabetes.
PG  - e2103495
LID - 10.1002/advs.202103495 [doi]
LID - 2103495
AB  - Type 2 diabetes mellitus (T2DM) is a systematic multi-organ metabolic disease, 
      which is characterized by the dynamic interplay among different organs. The 
      increasing incidence of T2DM reflects an urgent need for the development of in 
      vitro human-relevant models for disease study and drug therapy. Here, a new 
      microfluidic multi-organoid system is developed that recapitulates the human 
      liver-pancreatic islet axis in normal and disease states. The system contains two 
      compartmentalized regions connected by a microchannel network, enabling 3D 
      co-culture of human induced pluripotent stem cells (hiPSC)-derived liver and 
      islet organoids for up to 30 days under circulatory perfusion conditions. The 
      co-cultured liver and islet organoids exhibit favorable growth and improved 
      tissue-specific functions. Transcriptional analyses reveal the activation of 
      metabolically relevant signaling pathways in the co-cultured organoids. Notably, 
      the co-culture system facilitates sensitive glucose-stimulated insulin secretion 
      from islet organoids and increased glucose utilization in liver organoids by 
      glucose tolerance tests. Both liver and islet organoids display mitochondrial 
      dysfunction and decreased glucose transport capacity under high glucose 
      conditions, which can be alleviated by metformin treatment. This novel 
      multi-organoid system can recapitulate human-relevant liver-islet axis under both 
      physiological and pathological conditions, providing a unique platform for future 
      T2DM research and drug development.
CI  - (c) 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.
FAU - Tao, Tingting
AU  - Tao T
AD  - Division of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy 
      of Sciences, Dalian, 116023, China.
AD  - University of Chinese Academy of Sciences, Beijing, 100049, China.
FAU - Deng, Pengwei
AU  - Deng P
AD  - Division of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy 
      of Sciences, Dalian, 116023, China.
AD  - University of Chinese Academy of Sciences, Beijing, 100049, China.
FAU - Wang, Yaqing
AU  - Wang Y
AD  - Division of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy 
      of Sciences, Dalian, 116023, China.
FAU - Zhang, Xu
AU  - Zhang X
AD  - Division of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy 
      of Sciences, Dalian, 116023, China.
FAU - Guo, Yaqiong
AU  - Guo Y
AD  - Division of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy 
      of Sciences, Dalian, 116023, China.
AD  - University of Chinese Academy of Sciences, Beijing, 100049, China.
FAU - Chen, Wenwen
AU  - Chen W
AD  - Division of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy 
      of Sciences, Dalian, 116023, China.
AD  - University of Chinese Academy of Sciences, Beijing, 100049, China.
FAU - Qin, Jianhua
AU  - Qin J
AUID- ORCID: 0000-0001-5735-6436
AD  - Division of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy 
      of Sciences, Dalian, 116023, China.
AD  - Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 
      100101, China.
AD  - CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese 
      Academy of Sciences, Shanghai, 200031, China.
AD  - University of Chinese Academy of Sciences, Beijing, 100049, China.
LA  - eng
GR  - XDA16020900/the Strategic Priority Research Program of the Chinese Academy of 
      Science/
GR  - XDB29050301/the Strategic Priority Research Program of the Chinese Academy of 
      Science/
GR  - XDB32030200/the Strategic Priority Research Program of the Chinese Academy of 
      Science/
GR  - 2017YFB0405404/National Key R&D Program of China/
GR  - 202003AD150009/Yunnan Key Research and Development Program/
GR  - 31971373/National Nature Science Foundation of China/
GR  - Innovation Program of Science and Research from the DICP/
GR  - DICP I201934/CAS/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211223
PL  - Germany
TA  - Adv Sci (Weinh)
JT  - Advanced science (Weinheim, Baden-Wurttemberg, Germany)
JID - 101664569
SB  - IM
MH  - *Diabetes Mellitus, Type 2/metabolism
MH  - Humans
MH  - *Induced Pluripotent Stem Cells
MH  - *Islets of Langerhans
MH  - Liver
MH  - Organoids
PMC - PMC8844474
OTO - NOTNLM
OT  - hiPSCs
OT  - liver
OT  - multi-organoid-on-chip
OT  - pancreatic islet
COIS- The authors declare no conflict of interest.
EDAT- 2021/12/25 06:00
MHDA- 2022/04/08 06:00
PMCR- 2021/12/23
CRDT- 2021/12/24 06:12
PHST- 2021/11/21 00:00 [revised]
PHST- 2021/08/10 00:00 [received]
PHST- 2021/12/25 06:00 [pubmed]
PHST- 2022/04/08 06:00 [medline]
PHST- 2021/12/24 06:12 [entrez]
PHST- 2021/12/23 00:00 [pmc-release]
AID - ADVS3325 [pii]
AID - 10.1002/advs.202103495 [doi]
PST - ppublish
SO  - Adv Sci (Weinh). 2022 Feb;9(5):e2103495. doi: 10.1002/advs.202103495. Epub 2021 
      Dec 23.