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Cited by 582Pancreatic function and diabetesPluripotent Stem Cells ResearchDiabetes and associated disorders

Maturation of Human Embryonic Stem Cell–Derived Pancreatic Progenitors Into Functional Islets Capable of Treating Pre-existing Diabetes in Mice

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Rezania, Alireza, Bruin, Jennifer E., Riedel, Michael J., Mojibian, Majid, Asadi, Ali, Xu, Jean, Gauvin, Rebecca, Narayan, Kavitha +5 more·2012·Diabetes
DOI 10.2337/db11-1711PMC PMC3402300
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Abstract

Diabetes is a chronic debilitating disease that results from insufficient production of insulin from pancreatic β-cells. Islet cell replacement can effectively treat diabetes but is currently severely limited by the reliance upon cadaveric donor tissue. We have developed a protocol to efficiently differentiate commercially available human embryonic stem cells (hESCs) in vitro into a highly enriched PDX1+ pancreatic progenitor cell population that further develops in vivo to mature pancreatic endocrine cells. Immature pancreatic precursor cells were transplanted into immunodeficient mice with streptozotocin-induced diabetes, and glycemia was initially controlled with exogenous insulin. As graft-derived insulin levels increased over time, diabetic mice were weaned from exogenous insulin and human C-peptide secretion was eventually regulated by meal and glucose challenges. Similar differentiation of pancreatic precursor cells was observed after transplant in immunodeficient rats. Throughout the in vivo maturation period hESC-derived endocrine cells exhibited gene and protein expression profiles that were remarkably similar to the developing human fetal pancreas. Our findings support the feasibility of using differentiated hESCs as an alternative to cadaveric islets for treating patients with diabetes.

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  • ViaCyte developed a stem cell-derived pancreatic endoderm cell population known as PEC-01, which they demonstrated to mature over several months in vivo into insulin-producing endocrine cells in rodent models.

    “In particular, ViaCyte developed a stem cell-derived pancreatic endoderm cell population known as PEC-01, which they demonstrated to mature over several months in vivo into insulin-producing endocrine cells in rodent models.29–31”

    From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [30]

    The paper’s introductory discussion reports that ViaCyte transplanted hESC-derived pancreatic progenitors into mice and obtained mature, insulin-positive cells in vivo. It does not identify those cells as PEC-01 or specify that ViaCyte’s maturation took several months; the month-by-month results describe this paper’s own cells, not ViaCyte’s. (LLM, conf=0.83)

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Authors
Rezania, A., Bruin, J. E., Riedel, M. J., Mojibian, M., Asadi, A., Xu, J., Gauvin, R., Narayan, K., Karanu, F., O’Neil, J. J., Ao, Z., Warnock, G. L., & Kieffer, T. J.
Affiliations
  • Janssen Research & Development (United States) (US)
  • University of British Columbia (CA)
Corresponding author
Rezania, Alireza
ORCID
Venue
Diabetes
Publisher
American Diabetes Association
Published
2012-07-17
Volume
61
Issue
8
Pages
2016-2029
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
DOI
10.2337/db11-1711
PMC
PMC3402300
OpenAlex
W2132046208
Cited by
582
References
33
Citations by year
2026: 15 · 2025: 22 · 2024: 38 · 2023: 46 · 2022: 39 · 2021: 52 · 2020: 42 · 2019: 44 · 2018: 43 · 2017: 45 · 2016: 55 · 2015: 50 · 2014: 51 · 2013: 34 · 2012: 6
FWCI
45.92
Type
journal article
Language
en
Open access
Licence
Locations
  • Diabetes (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
Canadian Institutes of Health Research
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
human embryonic stem cells, pancreatic progenitor cells, pancreatic islet regeneration, diabetes treatment, PDX1, in vivo differentiation, islet transplantation, streptozotocin-induced diabetes, C-peptide secretion, insulin secretion
MeSH terms
Animals, Cell Differentiation, Cell Line, Diabetes Mellitus, Experimental, Humans, Insulin, Male, Pancreas, Stem Cells, Trans-Activators, Homeodomain Proteins, Proprotein Convertases, Insulin-Secreting Cells, Mice, Rats, Embryonic Stem Cells

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