Long-Term Culture of Self-renewing Pancreatic Progenitors Derived from Human Pluripotent Stem Cells
Open accessAbstract
Pluripotent stem cells have been proposed as an unlimited source of pancreatic β cells for studying and treating diabetes. However, the long, multi-step differentiation protocols used to generate functional β cells inevitably exhibit considerable variability, particularly when applied to pluripotent cells from diverse genetic backgrounds. We have developed culture conditions that support long-term self-renewal of human multipotent pancreatic progenitors, which are developmentally more proximal to the specialized cells of the adult pancreas. These cultured pancreatic progenitor (cPP) cells express key pancreatic transcription factors, including PDX1 and SOX9, and exhibit transcriptomes closely related to their in vivo counterparts. Upon exposure to differentiation cues, cPP cells give rise to pancreatic endocrine, acinar, and ductal lineages, indicating multilineage potency. Furthermore, cPP cells generate insulin+ β-like cells in vitro and in vivo, suggesting that they offer a convenient alternative to pluripotent cells as a source of adult cell types for modeling pancreatic development and diabetes.
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Several studies have demonstrated the ability to propagate the pancreatic progenitor population generated during the middle portion of the differentiation protocol.
“Several studies, however, have demonstrated the ability to propagate the pancreatic progenitor population that is generated during the middle portion of the differentiation protocol.181,182”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [181]
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- Authors
- Trott, J., Tan, E. K., Ong, S., Titmarsh, D. M., Denil, S. L. I. J., Giam, M., Wong, C. K., Wang, J., Shboul, M., Eio, M., Cooper-White, J., Cool, S. M., Rancati, G., Stanton, L. W., Reversade, B., & Dunn, N. R.
- Affiliations
- Agency for Science, Technology and Research (SG)
- The University of Queensland (AU)
- Corresponding author
- Trott, Jamie
- Dunn, N. Ray
- ORCID
- Venue
- Stem Cell Reports
- Publisher
- Elsevier BV
- Published
- 2017-06
- Volume
- 8
- Issue
- 6
- Pages
- 1675-1688
- ISSN
- 2213-6711 (ISSN-L)
- PMC
- PMC5470345
- OpenAlex
- W2621496209
- Cited by
- 77
- References
- 45
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 15 · 2023: 10 · 2022: 9 · 2021: 11 · 2020: 9 · 2019: 8 · 2018: 5 · 2017: 2
- FWCI
- 6.73
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Stem Cell Reports (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DR-NTU (Nanyang Technological University) (submittedVersion, cc-by-nc-nd)
- Funders
- Agency for Science, Technology and Research
- Economic Development Board - Singapore
- 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
- pancreatic progenitor cells, human pluripotent stem cells, self-renewal, long-term culture, beta cell differentiation, insulin-producing cells, PDX1, SOX9, pancreatic development, diabetes modeling, multilineage differentiation, pancreatic endocrine cells
- MeSH terms
- Cell Self Renewal, Animals, Cell Differentiation, Cell Line, Humans, Insulin, Kidney, Pancreas, Stem Cells, Transplantation, Heterologous, Trans-Activators, Down-Regulation, Mice, SCID, Mice, Inbred NOD, Homeodomain Proteins, Pluripotent Stem Cells, Insulin-Secreting Cells, Mice, SOX9 Transcription Factor, Feeder Cells
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