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Cited by 183Pancreatic function and diabetesPluripotent Stem Cells ResearchDiabetes and associated disorders

Gene-edited human stem cell–derived β cells from a patient with monogenic diabetes reverse preexisting diabetes in mice

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Maxwell, Kristina G., Augsornworawat, Punn, Velazco-Cruz, Leonardo, Kim, Michelle H., Asada, Rie, Hogrebe, Nathaniel J., Morikawa, Shuntaro, Urano, Fumihiko +1 more·2020·Science Translational Medicine
DOI 10.1126/scitranslmed.aax9106PMC PMC7233417
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Abstract

Patient stem cell–derived β cells corrected for a diabetes-causing variant in WFS1 restore glucose homeostasis when transplanted into diabetic mice.

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  • 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”

    From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [40]

  • Significant progress has been made at improving the function of SC-islets when compared to the original protocols.

    “To this end, significant progress has been made at improving the function of SC-islets when compared to the original protocols,39,40,44,48,49”

    From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [40]

  • SC-islets differentiated from iPSCs generated from a patient with Wolfram syndrome exhibited poor function and increased stress responses.

    “For example, SC-islets differentiated from iPSCs generated from a patient with Wolfram syndrome, which is characterized by ER stress, exhibited poor function and increased stress responses.40”

    From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [40]

  • Correcting the stress-causing pathogenic variant with CRISPR/Cas9 allowed the iPSC line to generate highly functional SC-islets capable of rapidly reversing severe diabetes in mice.

    “Correcting this stress-causing pathogenic variant with CRISPR/Cas9, however, allowed this iPSC line to generate highly functional SC-islets that were capable of rapidly reversing severe diabetes in mice, illustrating that gene-editing strategies can be used to mitigate stress responses.”

    From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [40]

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References 74 · Cited by 183

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Authors
Maxwell, K. G., Augsornworawat, P., Velazco-Cruz, L., Kim, M. H., Asada, R., Hogrebe, N. J., Morikawa, S., Urano, F., & Millman, J. R.
Affiliations
Washington University in St. Louis (US)
Corresponding author
  • Urano, Fumihiko
  • Millman, Jeffrey R.
ORCID
Venue
Science Translational Medicine
Publisher
American Association for the Advancement of Science (AAAS)
Published
2020-04-22
Volume
12
Issue
540
ISSN
  • 1946-6234 (ISSN-L)
  • 1946-6242
DOI
10.1126/scitranslmed.aax9106
PMC
PMC7233417
OpenAlex
W3018853840
Cited by
183
References
74
Citations by year
2026: 17 · 2025: 29 · 2024: 25 · 2023: 29 · 2022: 29 · 2021: 41 · 2020: 13
FWCI
25.59
Type
journal article
Language
en
Open access
Locations
  • Science Translational Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (UL1TR002345, UL1TR000448, P30CA91842)
  • National Institute of General Medical Sciences (R25GM103757)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK114233, R01DK112921, P30DK020579, T32DK108742, T32DK007120)
  • National Center for Advancing Translational Sciences (UH2TR002065)
  • Unravel Wolfram Syndrome Fund
  • Silberman Fund
  • Stowe Fund
  • Ellie White Foundation for Rare Genetic Disorders
  • Washington University Center of Regenerative Medicine
  • JDRF (5-CDA-2017-391-A-N)
  • Washington University School of Medicine in St. Louis
  • Manpei Suzuki Diabetes Foundation
  • Eye Hope Foundation
  • Snow Foundation
  • Feiock Fund
  • JSPS Overseas Research Fellowship
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
Wolfram syndrome, monogenic diabetes, stem cell-derived beta cells, CRISPR/Cas9 genome editing, induced pluripotent stem cells, beta cell differentiation, insulin secretion, streptozotocin-induced diabetes, diabetes reversal, endoplasmic reticulum stress, single-cell transcriptomics, autologous cell transplantation
MeSH terms
Gene Editing, Insulin Secretion, Animals, Cell Differentiation, Diabetes Mellitus, Humans, Insulin, Insulin-Secreting Cells, Mice, Induced Pluripotent Stem Cells

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