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An optimized protocol for efficient derivation of pancreatic islets from multiple human pluripotent stem cell lines

Wu, Siqin ; Chandel, Shivam ; Bryzgalova, Galyna ; Efstathopoulos, Paschalis ; Blust, Kelly ; Zhao, Cheng ; Erbil, Eda ; Falk, Anna LU orcid ; Hedhammar, My and Berggren, Per Olof , et al. (2026) In Stem Cell Reports 21(5).
Abstract

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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
beta cells, cell therapy, cell-line variability, diabetes, differentiation protocol, endocrine progenitors, endocrine purity, functional SC-islets, human pluripotent stem cells, intraocular transplantation
in
Stem Cell Reports
volume
21
issue
5
article number
102892
publisher
Cell Press
external identifiers
  • pmid:41997152
  • scopus:105035685232
ISSN
2213-6711
DOI
10.1016/j.stemcr.2026.102892
language
English
LU publication?
yes
id
5d40317f-f4fc-4578-9fb4-c426d0fdc71b
date added to LUP
2026-05-20 13:59:58
date last changed
2026-06-03 15:00:10
@article{5d40317f-f4fc-4578-9fb4-c426d0fdc71b,
  abstract     = {{<p>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.</p>}},
  author       = {{Wu, Siqin and Chandel, Shivam and Bryzgalova, Galyna and Efstathopoulos, Paschalis and Blust, Kelly and Zhao, Cheng and Erbil, Eda and Falk, Anna and Hedhammar, My and Berggren, Per Olof and Lanner, Fredrik}},
  issn         = {{2213-6711}},
  keywords     = {{beta cells; cell therapy; cell-line variability; diabetes; differentiation protocol; endocrine progenitors; endocrine purity; functional SC-islets; human pluripotent stem cells; intraocular transplantation}},
  language     = {{eng}},
  number       = {{5}},
  publisher    = {{Cell Press}},
  series       = {{Stem Cell Reports}},
  title        = {{An optimized protocol for efficient derivation of pancreatic islets from multiple human pluripotent stem cell lines}},
  url          = {{http://dx.doi.org/10.1016/j.stemcr.2026.102892}},
  doi          = {{10.1016/j.stemcr.2026.102892}},
  volume       = {{21}},
  year         = {{2026}},
}