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Cited by 38Pancreatic function and diabetesPluripotent Stem Cells ResearchDiabetes and associated disorders

Strategies to Improve the Safety of iPSC-Derived β Cells for β Cell Replacement in Diabetes

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Pellegrini, Silvia, Zamarian, Valentina, Sordi, Valeria·2022·Transplant International
DOI 10.3389/ti.2022.10575PMC PMC9448870
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Abstract

Allogeneic islet transplantation allows for the re-establishment of glycemic control with the possibility of insulin independence, but is severely limited by the scarcity of organ donors. However, a new source of insulin-producing cells could enable the widespread use of cell therapy for diabetes treatment. Recent breakthroughs in stem cell biology, particularly pluripotent stem cell (PSC) techniques, have highlighted the therapeutic potential of stem cells in regenerative medicine. An understanding of the stages that regulate β cell development has led to the establishment of protocols for PSC differentiation into β cells, and PSC-derived β cells are appearing in the first pioneering clinical trials. However, the safety of the final product prior to implantation remains crucial. Although PSC differentiate into functional β cells in vitro, not all cells complete differentiation, and a fraction remain undifferentiated and at risk of teratoma formation upon transplantation. A single case of stem cell-derived tumors may set the field back years. Thus, this review discusses four approaches to increase the safety of PSC-derived β cells: reprogramming of somatic cells into induced PSC, selection of pure differentiated pancreatic cells, depletion of contaminant PSC in the final cell product, and control or destruction of tumorigenic cells with engineered suicide genes.

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  • Concerns remain about less differentiated mitotic cells with the potential to form tumours in the transplant recipient.

    “Concerns remain about less differentiated mitotic cells with the potential to form tumours in the transplant recipient.74”

    From The future of type 1 diabetes therapy (2025) · cites this paper as [74]

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Authors
Pellegrini, S., Zamarian, V., & Sordi, V.
Affiliations
IRCCS Ospedale San Raffaele (IT)
Corresponding author
Sordi, Valeria
ORCID
Venue
Transplant International
Publisher
Frontiers Media SA
Published
2022-08-24
Volume
35
Pages
10575-10575
ISSN
  • 0934-0874 (ISSN-L)
  • 1432-2277
DOI
10.3389/ti.2022.10575
PMC
PMC9448870
OpenAlex
W4293163014
Cited by
38
References
148
Citations by year
2026: 9 · 2025: 12 · 2024: 13 · 2023: 4
FWCI
1.72
Type
journal article
Language
en
Open access
Licence
Locations
  • Transplant International (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
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
beta cell replacement, diabetes mellitus, cell therapy safety, teratoma risk, pluripotent stem cell differentiation, somatic cell reprogramming, allogeneic islet transplantation
MeSH terms
Cell Differentiation, Diabetes Mellitus, Humans, Insulin, Pluripotent Stem Cells, Insulin-Secreting Cells, Induced Pluripotent Stem Cells

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