Human assembloid of human blood vessel organoids with pancreatic islets improves insulin secretion over time ex vivo

Cell Rep. 2025 Oct 28;44(10):116378. doi: 10.1016/j.celrep.2025.116378. Epub 2025 Oct 3.

Abstract

Pancreatic islet transplantation is a promising treatment strategy for type 1 diabetes patients; however, there are still major challenges to overcome, including vascularization. Despite a substantial need to understand the islet graft decline observed in patients 5-10 years post transplantation, clinical translation remains challenging, probably because of species-specific features and the lack of in vitro vascularized models. Here, we report results of a human assembloid composed of self-organizing 3D blood vessel organoids (BVOs) with human pancreatic islets. We demonstrate that co-culture of islets and BVOs ex vivo leads to an auto-organized assembloid (by light-sheet fluorescence microscopy) and improves insulin secretion over time (functionality assays) on 5 independent human islet donors (from 3 different hospital facilities). Taken together, this study could accelerate our understanding of type 1 diabetes and facilitate therapeutic development for type 1 diabetes patients.

Keywords: CP: Stem cell research; assembloid; blood vessel organoid; islet transplantation; pancreas; type 1 diabetes.

MeSH terms

  • Blood Vessels* / cytology
  • Blood Vessels* / metabolism
  • Coculture Techniques
  • Diabetes Mellitus, Type 1
  • Humans
  • Insulin Secretion*
  • Insulin* / metabolism
  • Islets of Langerhans Transplantation / methods
  • Islets of Langerhans* / cytology
  • Islets of Langerhans* / metabolism
  • Organoids* / cytology
  • Organoids* / metabolism

Substances

  • Insulin