Microengineered Multi‐Organoid System from hiPSCs to Recapitulate Human Liver‐Islet Axis in Normal and Type 2 Diabetes

Abstract: 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.

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch

Erschienen in
Microengineered Multi‐Organoid System from hiPSCs to Recapitulate Human Liver‐Islet Axis in Normal and Type 2 Diabetes ; day:23 ; month:12 ; year:2021 ; extent:13
Advanced science ; (23.12.2021) (gesamt 13)

Urheber
Tao, Tingting
Deng, Pengwei
Wang, Yaqing
Zhang, Xu
Guo, Yaqiong
Chen, Wenwen
Qin, Jianhua

DOI
10.1002/advs.202103495
URN
urn:nbn:de:101:1-2021122414145479485904
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
15.08.2025, 07:27 MESZ

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Beteiligte

  • Tao, Tingting
  • Deng, Pengwei
  • Wang, Yaqing
  • Zhang, Xu
  • Guo, Yaqiong
  • Chen, Wenwen
  • Qin, Jianhua

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