Development of a vascularized multi-organoid-on-a-chip to model the heart-islet axis in diabetic cardiomyopathy

  • Bioact Mater. 2026 May 28:64:867-882. doi: 10.1016/j.bioactmat.2026.05.033.
Zhuangzhuang Yang  1 ,  Lei Lin  1 ,  Jinxiu Jiang  1 ,  Yiran Wang  1 ,  Feiyi Li  1 ,  Xinyue Li  1 ,  Jiali Fang  2 ,  Lilin Xu  1 ,  Hao Li  1 ,  Liqian Du  1 ,  Zhaoce Liu  3 ,  Rui Liang  3 ,  Shusen Wang  3 ,  Xianhao Dong  1 ,  Shijun Hu  4 ,  Yajun Duan  5 ,  Hua Qin  2 ,  Deling Kong  1  6
Affiliations
  • 1. State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for Cell Responses, Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin, 300071, China.
  • 2. State Key Laboratory of Medicinal Chemical Biology, Institute of Immunology, College of Life Sciences, Nankai University, Tianjin, 300071, China.
  • 3. Department of Cellular Therapy, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, 300071, China.
  • 4. Department of Cardiovascular Surgery of the First Affiliated Hospital & Institute for Cardiovascular Science, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Protection, Suzhou Medical College, Soochow University, Suzhou, 215000, China.
  • 5. Department of Cardiology, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, China.
  • 6. Nankai International Advanced Research Institute (Shenzhen Futian), Nankai University, Shenzhen, Guangdong, 518045, China.
PMID: 42253918 DOI: 10.1016/j.bioactmat.2026.05.033
Abstract

The dynamic crosstalk between pancreatic islets and the heart plays a critical yet poorly understood role in diabetic cardiomyopathy (DCM). Here, we present a vascularized multi-organoid-on-a-chip platform that enables the perfusion co-culture of human iPSC-derived vascularized cardiac organoids (VCOs) and vascularized islet organoids (VIOs). Under a gradient of hyperglycemic stress, this system recapitulated key features of DCM, including cardiomyocyte structural disassembly and vascular dysfunction. Crucially, co-culture with functional VIOs provided substantial protection against hyperglycemia, mitigating cardiac damage by restoring metabolic and contractile gene programs. Our study establishes a modular and physiologically relevant model to dissect the dose-dependent protective role of islets in diabetic heart disease and to screen for interventions targeting inter-organ communication.

Keywords
Cardiac organoid; Diabetic cardiomyopathy; Islet organoid; Organ-on-a-Chip; Vascularized organoid.
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