Cited by 41Pancreatic function and diabetesPluripotent Stem Cells ResearchDiabetes and associated disorders

Characterization of stem-cell-derived islets during differentiation and after implantation

Open access
Cuesta-Gomez, Nerea, Verhoeff, Kevin, Jasra, Ila Tewari, Pawlick, Rena, Dadheech, Nidheesh, Shapiro, A.M. James·2022·Cell Reports

Abstract

Recapitulation of embryonic pancreatic development has enabled development of methods for in vitro islet cell differentiation using human pluripotent stem cells (hPSCs), which have the potential to cure diabetes. Advanced methods for optimal generation of stem-cell-derived islets (SC-islets) has enabled successful diabetes reversal in rodents and shown promising early clinical trial outcomes. The main impediment for use of SC-islets is concern about safety because of off-target growth resulting from contaminated residual cells. In this review, we summarize the different endocrine and non-endocrine cell populations that have been described to emerge throughout β cell differentiation and after transplantation. We discuss the most recent approaches to enrich endocrine populations and remove off-target cells. Finally, we discuss the critical quality control and release criteria testing that we anticipate will be required prior to transplantation to ensure product safety.

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Crossref · 10.1016/j.celrep.2022.111238

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  • With less optimized protocols or cell lines, there is potential to retain progenitor cells in the final islet clusters as well as produce other endodermal cell types, such as those of hepatic origin.

    “With less optimized protocols or cell lines, there is also the potential to retain progenitor cells in the final islet clusters as well as produce other endodermal cell types, such as those of hepatic origin.39,58”

    From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [58]

    The Introduction (page unavailable) says stem-cell-derived islets can retain progenitors and describes non-pancreatic endodermal tissues arising from contaminating cells, particularly gastrointestinal and respiratory epithelia. It does not identify cells of hepatic origin, so that example is not supported by this source. (LLM, conf=0.86)

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Research works printed but not linked: 2

  1. [9]9. Aye, M.M. ∙ Atkin, S.L. Patient safety and minimizing risk with insulin administration - role of insulin degludec Drug Healthc. Patient Saf. 2014; 6:55-67 PubMed Google Scholar
  2. [16]16. Blum, B. ∙ Hrvatin, S. ∙ Schuetz, C. ... Functional beta-cell maturation is marked by an increased glucose threshold and by expression of urocortin 3 Nat. Biotechnol. 2012; 30:261-264 Crossref Scopus (287) PubMed Google Scholar

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Authors
Cuesta-Gomez, N., Verhoeff, K., Jasra, I. T., Pawlick, R., Dadheech, N., & Shapiro, A. M. J.
Affiliations
University of Alberta (CA)
Corresponding author
  • Dadheech, Nidheesh
  • Shapiro, A.M. James
Venue
Cell Reports
Publisher
Elsevier BV
Published
2022-08
Volume
40
Issue
8
Pages
111238
ISSN
2211-1247 (ISSN-L)
OpenAlex
W4292755723
Cited by
41
References
75
Citations by year
2026: 9 · 2025: 12 · 2024: 10 · 2023: 9 · 2022: 1
FWCI
1.91
Type
journal article
Language
en
Open access
Locations
  • Cell Reports (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • Canada Research Chairs
  • Alberta Diabetes Foundation
  • Juvenile Diabetes Research Foundation Canada
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
Keywords
stem cell-derived islets, human pluripotent stem cells, islet cell differentiation, pancreatic development, beta cell differentiation, islet transplantation, diabetes mellitus, quality control, cell therapy safety
MeSH terms
Cell Differentiation, Humans, Islets of Langerhans, Pancreas, Islets of Langerhans Transplantation, Pluripotent Stem Cells

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