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Cited by 1,843Pancreatic function and diabetesPluripotent Stem Cells ResearchDiabetes and associated disorders

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Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo

Kroon, Evert, Martinson, Laura A, Kadoya, Kuniko, Bang, Anne G, Kelly, Olivia G, Eliazer, Susan, Young, Holly, Richardson, Mike, Smart, Nora G, Cunningham, Justine, Agulnick, Alan D, D'Amour, Kevin A, Carpenter, Melissa K, Baetge, Emmanuel E·2008·Nature Biotechnology
DOI 10.1038/nbt1393
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Abstract

Development of a cell therapy for diabetes would be greatly aided by a renewable supply of human beta-cells. Here we show that pancreatic endoderm derived from human embryonic stem (hES) cells efficiently generates glucose-responsive endocrine cells after implantation into mice. Upon glucose stimulation of the implanted mice, human insulin and C-peptide are detected in sera at levels similar to those of mice transplanted with approximately 3,000 human islets. Moreover, the insulin-expressing cells generated after engraftment exhibit many properties of functional beta-cells, including expression of critical beta-cell transcription factors, appropriate processing of proinsulin and the presence of mature endocrine secretory granules. Finally, in a test of therapeutic potential, we demonstrate that implantation of hES cell-derived pancreatic endoderm protects against streptozotocin-induced hyperglycemia. Together, these data provide definitive evidence that hES cells are competent to generate glucose-responsive, insulin-secreting cells.

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Metadata

Authors
Kroon, E., Martinson, L. A., Kadoya, K., Bang, A. G., Kelly, O. G., Eliazer, S., Young, H., Richardson, M., Smart, N. G., Cunningham, J., Agulnick, A. D., D'Amour, K. A., Carpenter, M. K., & Baetge, E. E.
ORCID
Venue
Nature Biotechnology
Publisher
Springer Science and Business Media LLC
Published
2008-02-20
Volume
26
Issue
4
Pages
443-452
ISSN
  • 0733-222X (ISSN-L)
  • 1087-0156
  • 1546-1696
DOI
10.1038/nbt1393
OpenAlex
W2106219965
Cited by
1,843
References
0
Citations by year
2026: 26 · 2025: 44 · 2024: 46 · 2023: 88 · 2022: 67 · 2021: 81 · 2020: 85 · 2019: 76 · 2018: 87 · 2017: 98 · 2016: 122 · 2015: 116 · 2014: 156 · 2013: 168 · 2012: 154
FWCI
150.73
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Biotechnology (publishedVersion)
  • PubMed (publishedVersion)
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
human embryonic stem cells, beta cell differentiation, glucose-dependent insulin secretion, islet transplantation, diabetes cell therapy, C-peptide, proinsulin processing, streptozotocin-induced hyperglycemia
MeSH terms
Animals, Cell Differentiation, Cells, Cultured, Endoderm, Glucose, Humans, Insulin, Cell Culture Techniques, Pancreas, Artificial, Tissue Engineering, Cell Proliferation, Insulin-Secreting Cells, Mice, Embryonic Stem Cells

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