An optimized protocol for efficient derivation of pancreatic islets from multiple human pluripotent stem cell lines
Summary
The success of cell therapy for type 1 diabetes (T1D) depends on reliable differentiation of stem cells into functional pancreatic islets. Current protocols produce stem cell-derived islets (SC-islets) that contain non-endocrine cells and show limited maturity. We developed a robust protocol that generates functional SC-islets from all eight tested human pluripotent stem cell (hPSC) lines. Differentiation to the endocrine progenitor (EP) stage on 2D laminin-521 is improved by shortening the prior pancreatic progenitor (PP) stage. Notably, allowing EP cells to self-aggregate efficiently removes proliferative and non-endocrine cells. Subsequent suspension culture yields SC-islets with strong glucose responsiveness in vitro. After transplantation into the anterior chamber of the eye of diabetic mice, SC-islets further mature and restore normal glycemic control. Single-cell analyses show that the SC-islets are free of non-endocrine cell populations before and after transplantation. This protocol enables production of highly functional SC-islets suitable for T1D cell therapy. Copyright © 2026 The Authors. Published by Elsevier Inc. All rights reserved.
| Authors | Wu S, Chandel S, Bryzgalova G, Efstathopoulos P, Blust K, Zhao C, Erbil E, Falk A, Hedhammar M, Berggren PO, Lanner F |
|---|---|
| Journal | Stem cell reports |
| Publication Date | 2026 May 12;21(5):102892 |
| PubMed | 41997152 |
| PubMed Central | PMC13163220 |
| DOI | 10.1016/j.stemcr.2026.102892 |