Human assembloid of human blood vessel organoids with pancreatic islets improves insulin secretion over time ex vivo
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.
Authors
- Thomas Domet (ORCID: https://orcid.org/0000-0003-3044-0819)
- Sabrina Granziera (ORCID: https://orcid.org/0009-0006-7653-8204)
- Karim Bouzakri (ORCID: https://orcid.org/0000-0002-0703-5105)
- Mahira Mehanović (ORCID: https://orcid.org/0000-0002-6210-787X)
- W. Bietiger
- Stéphanie Combe (ORCID: https://orcid.org/0009-0006-7847-0493)
- Delphine Freida (ORCID: https://orcid.org/0009-0001-4818-713X)
- Josef Penninger (ORCID: https://orcid.org/0000-0002-8194-3777)
- Emily Tubbs (ORCID: https://orcid.org/0000-0003-4925-9374)
- Clément Quintard (ORCID: https://orcid.org/0000-0003-4202-5399)
- Mélanie Lopes (ORCID: https://orcid.org/0009-0001-5665-4826)
- Mathieu Armanet (ORCID: https://orcid.org/0000-0001-6494-3380)
- Xavier Gidrol (ORCID: https://orcid.org/0000-0002-4233-3749)
- Julia Sabatier
- Clara Pirlian
Institutions
- University of British Columbia (CA)
- Inserm (FR)
- European Science Foundation (FR)
- Université Paris Cité (FR)
- Commissariat à l'Énergie Atomique et aux Énergies Alternatives (FR)
- CEA Grenoble (FR)
- Institute for Regenerative Medicine & Biotherapy (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Hôpital Saint-Louis (FR)
- Medical University of Vienna (AT)
- Université Grenoble Alpes (FR)
Publication Details
- Journal
- Cell Reports
- Published
- 2025-10-01
- DOI
- https://doi.org/10.1016/j.celrep.2025.116378
- Citations
- 5
- Primary Topic
- Pancreatic function and diabetes
- Type
- article
- Field-Weighted Citation Impact
- 10.03