The DOI matches its Crossref record; 56 of the 57 references it cites were found in a registry or an index.
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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Projections of Global Mortality and Burden of Disease from 2002 to 2030
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Method for the Isolation of Intact Islets of Langerhans from the Rat Pancreas
Lacy, P. E., & Kostianovsky, M. (1967) · Diabetes · doi:10.2337/diab.16.1.35 · Cited by 2,741
Generation of Functional Human Pancreatic β Cells In Vitro
Pagliuca, F. W., Millman, J. R., Gürtler, M., Segel, M., Van Dervort, A., Ryu, J. H., Peterson, Q. P., Greiner, D., & Melton, D. A. (2014) · Cell · doi:10.1016/j.cell.2014.09.040 · Cited by 2,025
Self-citationInternational trial of the Edmonton protocol for islet transplantation
Shapiro, A. M. J., Ricordi, C., Hering, B. J., Auchincloss, H., Lindblad, R., Robertson, R. P., Secchi, A., Brendel, M. D., Berney, T., Brennan, D. C., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa061267 · Cited by 1,942
Production of pancreatic hormone–expressing endocrine cells from human embryonic stem cells
D’Amour, K. A., Bang, A. G., Eliazer, S., Kelly, O., Agulnick, A. D., Smart, N. G., Moorman, M. A., KROON, E. J., Carpenter, M. K., & Baetge, E. E. (2006) · Nature Biotechnology · doi:10.1038/nbt1259 · Cited by 1,913
Kroon, E., Martinson, L. A., Kadoya, K., Bang, A. G., Kelly, O. G., Eliazer, S., Young, H., Richardson, M., Smart, N. G., Cunningham, J., et al. (2008) · Nature Biotechnology · doi:10.1038/nbt1393 · Cited by 1,843 · cited 2×
“Through modulation of pathways identified from embryonic development, studies with hPSCs have detailed protocols for generating cells that resemble early endoderm and pancreatic progenitors (D’Amour et al., 2006; D’Amour et al., 2005; Kroon et al., 2008; Nostro et al., 2015; Rezania et al., 2012), the latter of which…”
BackgroundEfficient differentiation of human embryonic stem cells to definitive endoderm
D'Amour, K. A., Agulnick, A. D., Eliazer, S., Kelly, O. G., Kroon, E., & Baetge, E. E. (2005) · Nature Biotechnology · doi:10.1038/nbt1163 · Cited by 1,730
Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells
Rezania, A., Bruin, J. E., Arora, P., Rubin, A., Batushansky, I., Asadi, A., O'Dwyer, S., Quiskamp, N., Mojibian, M., Albrecht, T., et al. (2014) · Nature Biotechnology · doi:10.1038/nbt.3033 · Cited by 1,575
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Single‐cell RNA sequencing technologies and applications: A brief overview
Jovic, D., Liang, X., Zeng, H., Lin, L., Xu, F., & Luo, Y. (2022) · Clinical and Translational Medicine · doi:10.1002/ctm2.694 · Cited by 1,379
Balboa, D., Barsby, T., Lithovius, V., Saarimäki-Vire, J., Omar-Hmeadi, M., Dyachok, O., Montaser, H., Lund, P.-E., Yang, M., Ibrahim, H., et al. (2022) · Nature Biotechnology · doi:10.1038/s41587-022-01219-z · Cited by 433
Targeting the cytoskeleton to direct pancreatic differentiation of human pluripotent stem cells
Hogrebe, N. J., Augsornworawat, P., Maxwell, K. G., Velazco-Cruz, L., & Millman, J. R. (2020) · Nature Biotechnology · doi:10.1038/s41587-020-0430-6 · Cited by 373
Self-citationGeneration of insulin-producing pancreatic β cells from multiple human stem cell lines
Hogrebe, N. J., Maxwell, K. G., Augsornworawat, P., & Millman, J. R. (2021) · Nature Protocols · doi:10.1038/s41596-021-00560-y · Cited by 211
Self-citationDevelopments in stem cell-derived islet replacement therapy for treating type 1 diabetes
Hogrebe, N. J., Ishahak, M., & Millman, J. R. (2023) · Cell Stem Cell · doi:10.1016/j.stem.2023.04.002 · Cited by 210
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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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