Modeling in vivo induction of gastric insulin-secreting cells using transplanted human stomach organoids
Year: 2025
Type: article
Abstract: Insulin-dependent diabetes could be treated by supplying patients with primary pancreatic islets or other types of insulin-secreting cells. Functional insulin-secreting cells can be induced in situ from the murine stomach using defined genetic factors, offering a promising method to directly produce autologous insulin-secreting cells. Here, we modeled whether such gastric insulin-secreting (GINS) cells could be generated in vivo from human stomach tissues. We produced human gastric organoids (hGOs) from human embryonic stem cells engineered with inducible expression of reprogramming factors. The hGOs were stably transplanted for 6 months and showed robust cytodifferentiation resembling the human stomach in structure and cellular composition. Upon hGO maturation in vivo , we activated the reprogramming factors and observed the formation of insulin + cells, which secreted insulin into the circulation and ameliorated experimental diabetes. Our modeling indicates that GINS cells can be induced from human stomach tissues in vivo , warranting further therapeutic development for this technology.
Source: Stem Cell Reports
Authors: Jiaqi Lu, Hyunkee Kim, Jian Zhu, Capucine Martin, Jiaoyue Zhang, Vasumati Polavarapu, Lauretta A. Lacko, Chaiyaboot Ariyachet, Anna A. Dattoli, Tao Liu, Xia Chen, Qing Xia, Xiaofeng Huang, Qiao Zhou
Institutions: Harvard University, Peking University, National Medical Products Administration, State Key Laboratory of Natural and Biomimetic Drugs, Jiangnan University, Wuxi Fourth People's Hospital, Weill Cornell Medicine, Huazhong University of Science and Technology, Weill Cornell Medical Center, Chulalongkorn University
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,190
OpenAlex ID: W4415964651