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

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

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

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.stemcr.2018.12.012

Cites

56 of 56 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Transplantation of SC-islets into mice improves their insulin secretion and glucose responsiveness, suggesting that SC-islet immaturity can be resolved.

    “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]

    The Results section, “Transplantation of SC-β Cells into Glucose-Intolerant Mice” (page unavailable), reports glucose-responsive human insulin secretion after transplantation and improved glucose tolerance in recipient mice. But it does not show that transplantation improved the cells’ insulin secretion or glucose responsiveness relative to before transplantation. The Discussion instead attributes enhanced functional maturation to the six-stage differentiation strategy, so the claim that transplantation resolves immaturity is not supported. (LLM, conf=0.86)

    Experimental — accuracy not yet measured
  • These SC-β cells have been shown to improve glycemic control in diabetic mice.

    “These cells have been shown to improve glycemic control in diabetic mice, highlighting their potential utility in vivo.36,37,39–44”

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

1 of the 57 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

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.
Venue
Stem Cell Reports
Publisher
Elsevier BV
Published
2019-02
Volume
12
Issue
2
Pages
351-365
ISSN
2213-6711 (ISSN-L)
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
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 › 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
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review