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Acquisition of Dynamic Function in Human Stem Cell-Derived β Cells
Open accessAbstract
Recent advances in human pluripotent stem cell (hPSC) differentiation protocols have generated insulin-producing cells resembling pancreatic β cells. While these stem cell-derived β (SC-β) cells are capable of undergoing glucose-stimulated insulin secretion (GSIS), insulin secretion per cell remains low compared with islets and cells lack dynamic insulin release. Herein, we report a differentiation strategy focused on modulating transforming growth factor β (TGF-β) signaling, controlling cellular cluster size, and using an enriched serum-free media to generate SC-β cells that express β cell markers and undergo GSIS with first- and second-phase dynamic insulin secretion. Transplantation of these cells into mice greatly improves glucose tolerance. These results reveal that specific time frames for inhibiting and permitting TGF-β signaling are required during SC-β cell differentiation to achieve dynamic function. The capacity of these cells to undergo GSIS with dynamic insulin release makes them a promising cell source for diabetes cellular therapy.
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“Transplantation of SC-islets into mice improves their insulin secretion and glucose responsiveness, suggesting that SC-islet immaturity can be resolved.”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [42]
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“These cells have been shown to improve glycemic control in diabetic mice, highlighting their potential utility in vivo.36,37,39–44”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [42]
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Metadata
- Authors
- Velazco-Cruz, L., Song, J., Maxwell, K. G., Goedegebuure, M. M., Augsornworawat, P., Hogrebe, N. J., & Millman, J. R.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Millman, Jeffrey R.
- ORCID
- Venue
- Stem Cell Reports
- Publisher
- Elsevier BV
- Published
- 2019-02
- Volume
- 12
- Issue
- 2
- Pages
- 351-365
- ISSN
- 2213-6711 (ISSN-L)
- PMC
- PMC6372986
- OpenAlex
- W2910245538
- Cited by
- 399
- References
- 57
- Citations by year
- 2026: 45 · 2025: 49 · 2024: 54 · 2023: 56 · 2022: 61 · 2021: 72 · 2020: 42 · 2019: 20
- FWCI
- 46.82
- 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)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- NIH (5R01DK114233, 5P30DK020579, 2R25GM103757, 5T32DK108742, 5T32DK007120)
- JDRF (5-CDA-2017-391-A-N)
- Washington University Center of Regenerative Medicine
- Washington University School of Medicine
- Hope Center Viral Vectors Core
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › 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 beta cells, human pluripotent stem cells, glucose-stimulated insulin secretion, TGF-beta signaling, beta cell differentiation, serum-free medium, islet transplantation, glucose tolerance, diabetes cell therapy
- MeSH terms
- Animals, Cell Differentiation, Cells, Cultured, Glucose, Humans, Insulin, Pancreas, Signal Transduction, Transforming Growth Factor beta, Pluripotent Stem Cells, Insulin-Secreting Cells, Mice, Embryonic Stem Cells, Cell- and Tissue-Based Therapy
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