Cited by 406Pancreatic function and diabetesPluripotent Stem Cells ResearchDiabetes and associated disorders

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Acquisition of Dynamic Function in Human Stem Cell-Derived β Cells

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Velazco-Cruz, Leonardo, Song, Jiwon, Maxwell, Kristina G., Goedegebuure, Madeleine M., Augsornworawat, Punn, Hogrebe, Nathaniel J., Millman, Jeffrey R.·2019·Stem Cell Reports

DOI 10.1016/j.stemcr.2018.12.012PMC PMC6372986

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Abstract

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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Additional file 1 of Using single-nucleus RNA-sequencing to interrogate transcriptomic profiles of archived human pancreatic islets
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Additional file 2 of Metabolic switching, growth kinetics and cell yields in the scalable manufacture of stem cell-derived insulin-producing cells
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Additional file 1 of Comparative and integrative single cell analysis reveals new insights into the transcriptional immaturity of stem cell-derived β cells
Schmidt, M. D., Ishahak, M., Augsornworawat, P., & Millman, J. R. (2024) · Figshare · doi:10.6084/m9.figshare.26672244
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Additional file 2 of Comparative and integrative single cell analysis reveals new insights into the transcriptional immaturity of stem cell-derived β cells
Schmidt, M. D., Ishahak, M., Augsornworawat, P., & Millman, J. R. (2024) · Figshare · doi:10.6084/m9.figshare.26672247
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Additional file 7 of Comparative and integrative single cell analysis reveals new insights into the transcriptional immaturity of stem cell-derived β cells
Schmidt, M. D., Ishahak, M., Augsornworawat, P., & Millman, J. R. (2024) · Figshare · doi:10.6084/m9.figshare.26672262
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Additional file 3 of Comparative and integrative single cell analysis reveals new insights into the transcriptional immaturity of stem cell-derived β cells
Schmidt, M. D., Ishahak, M., Augsornworawat, P., & Millman, J. R. (2024) · Figshare · doi:10.6084/m9.figshare.26672250
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Additional file 4 of Metabolic switching, growth kinetics and cell yields in the scalable manufacture of stem cell-derived insulin-producing cells
Iworima, D. G., Baker, R. K., Ellis, C. E., Sherwood, C., Zhan, L., Rezania, A., Piret, J. M., & Kieffer, T. J. (2024) · Figshare · doi:10.6084/m9.figshare.26659423
Additional file 2 of Using single-nucleus RNA-sequencing to interrogate transcriptomic profiles of archived human pancreatic islets
Basile, G., Kahraman, S., Dirice, E., Pan, H., Dreyfuss, J. M., & Kulkarni, R. N. (2021) · Figshare · doi:10.6084/m9.figshare.15145904
Additional file 3 of Metabolic switching, growth kinetics and cell yields in the scalable manufacture of stem cell-derived insulin-producing cells
Iworima, D. G., Baker, R. K., Ellis, C. E., Sherwood, C., Zhan, L., Rezania, A., Piret, J. M., & Kieffer, T. J. (2024) · Figshare · doi:10.6084/m9.figshare.26659420
Additional file 6 of Comparative and integrative single cell analysis reveals new insights into the transcriptional immaturity of stem cell-derived β cells
Schmidt, M. D., Ishahak, M., Augsornworawat, P., & Millman, J. R. (2024) · Figshare · doi:10.6084/m9.figshare.26672259
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Additional file 5 of Metabolic switching, growth kinetics and cell yields in the scalable manufacture of stem cell-derived insulin-producing cells
Iworima, D. G., Baker, R. K., Ellis, C. E., Sherwood, C., Zhan, L., Rezania, A., Piret, J. M., & Kieffer, T. J. (2024) · Figshare · doi:10.6084/m9.figshare.26659426
Additional file 5 of Comparative and integrative single cell analysis reveals new insights into the transcriptional immaturity of stem cell-derived β cells
Schmidt, M. D., Ishahak, M., Augsornworawat, P., & Millman, J. R. (2024) · Figshare · doi:10.6084/m9.figshare.26672256
Self-citation
Additional file 4 of Using single-nucleus RNA-sequencing to interrogate transcriptomic profiles of archived human pancreatic islets
Basile, G., Kahraman, S., Dirice, E., Pan, H., Dreyfuss, J. M., & Kulkarni, R. N. (2021) · Figshare · doi:10.6084/m9.figshare.15145910
Additional file 8 of Metabolic switching, growth kinetics and cell yields in the scalable manufacture of stem cell-derived insulin-producing cells
Iworima, D. G., Baker, R. K., Ellis, C. E., Sherwood, C., Zhan, L., Rezania, A., Piret, J. M., & Kieffer, T. J. (2024) · Figshare · doi:10.6084/m9.figshare.26659435
Additional file 7 of Metabolic switching, growth kinetics and cell yields in the scalable manufacture of stem cell-derived insulin-producing cells
Iworima, D. G., Baker, R. K., Ellis, C. E., Sherwood, C., Zhan, L., Rezania, A., Piret, J. M., & Kieffer, T. J. (2024) · Figshare · doi:10.6084/m9.figshare.26659432
Additional file 3 of Using single-nucleus RNA-sequencing to interrogate transcriptomic profiles of archived human pancreatic islets
Basile, G., Kahraman, S., Dirice, E., Pan, H., Dreyfuss, J. M., & Kulkarni, R. N. (2021) · Figshare · doi:10.6084/m9.figshare.15145907
Additional file 1 of Metabolic switching, growth kinetics and cell yields in the scalable manufacture of stem cell-derived insulin-producing cells
Iworima, D. G., Baker, R. K., Ellis, C. E., Sherwood, C., Zhan, L., Rezania, A., Piret, J. M., & Kieffer, T. J. (2024) · Figshare · doi:10.6084/m9.figshare.26659414
Additional file 4 of Comparative and integrative single cell analysis reveals new insights into the transcriptional immaturity of stem cell-derived β cells
Schmidt, M. D., Ishahak, M., Augsornworawat, P., & Millman, J. R. (2024) · Figshare · doi:10.6084/m9.figshare.26672253
Self-citation
Additional file 6 of Metabolic switching, growth kinetics and cell yields in the scalable manufacture of stem cell-derived insulin-producing cells
Iworima, D. G., Baker, R. K., Ellis, C. E., Sherwood, C., Zhan, L., Rezania, A., Piret, J. M., & Kieffer, T. J. (2024) · Figshare · doi:10.6084/m9.figshare.26659429
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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: Velazco-Cruz, Leonardo
Song, Jiwon
Maxwell, Kristina G.
Goedegebuure, Madeleine M.
Augsornworawat, Punn
Hogrebe, Nathaniel J.
Millman, Jeffrey R.
Venue: Stem Cell Reports
Publisher: Elsevier BV
Published: 2019-02
Volume: 12
Issue: 2
Pages: 351-365
ISSN: 2213-6711 (ISSN-L)
DOI: 10.1016/j.stemcr.2018.12.012
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: cc-by-nc-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by-nc-nd/4.0/ (vor)
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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Acquisition of Dynamic Function in Human Stem Cell-Derived β Cells

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