Emerging routes to the generation of functional β-cells for diabetes mellitus cell therapy
Open accessAbstract
Diabetes mellitus, which affects more than 463 million people globally, is caused by the autoimmune ablation or functional loss of insulin-producing β-cells, and prevalence is projected to continue rising over the next decades. Generating β-cells to mitigate the aberrant glucose homeostasis manifested in the disease has remained elusive. Substantial advances have been made in producing mature β-cells from human pluripotent stem cells that respond appropriately to dynamic changes in glucose concentrations in vitro and rapidly function in vivo following transplantation in mice. Other potential avenues to produce functional β-cells include: transdifferentiation of closely related cell types (for example, other pancreatic islet cells such as α-cells, or other cells derived from endoderm); the engineering of non-β-cells that are capable of modulating blood sugar; and the construction of synthetic 'cells' or particles mimicking functional aspects of β-cells. This Review focuses on the current status of generating β-cells via these diverse routes, highlighting the unique advantages and challenges of each approach. Given the remarkable progress in this field, scalable bioengineering processes are also discussed for the realization of the therapeutic potential of derived β-cells.
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Both xenotransplantation with porcine islets and human stem cells are under investigation to solve the problem of limited availability of donors for pancreas or islet transplantation.
“Both xenotransplantation with porcine islets and human stem cells are under investigation to solve the problem of limited availability of donors for pancreas or islet transplantation (287).”
From The management of type 1 diabetes in adults. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) (2021) · cites this paper as [287]
The Abstract (page not provided) identifies scarce donor tissue as a barrier to islet transplantation and describes efforts to generate β-cells from human pluripotent stem cells. The section “Directed differentiation from hPSCs” also discusses these cells as a potential therapeutic source. Our copy does not support the other attributed approach: xenotransplantation with porcine islets (searched: porcine, xenotransplantation). (LLM, conf=0.88)
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- Authors
- Nair, G. G., Tzanakakis, E. S., & Hebrok, M.
- Affiliations
- University of California, San Francisco (US)
- Tufts University (US)
- Corresponding author
- Hebrok, Matthias
- Venue
- Nature Reviews Endocrinology
- Published
- 2020-06-25
- Volume
- 16
- Issue
- 9
- Pages
- 506-518
- ISSN
- 1759-5029 (ISSN-L)
- 1759-5037
- PMC
- PMC9188823
- OpenAlex
- W3037769443
- Cited by
- 134
- References
- 21
- Citations by year
- 2026: 17 · 2025: 16 · 2024: 13 · 2023: 28 · 2022: 27 · 2021: 29 · 2020: 4
- FWCI
- 4.98
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Reviews Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK060533, R01DK105831)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Keywords
- diabetes mellitus, cell therapy, pluripotent stem cells, transdifferentiation, pancreatic islet cells, alpha cells, artificial cells, glucose homeostasis, beta cell transplantation
- MeSH terms
- Animals, Blastocyst, Cell Differentiation, Diabetes Mellitus, Humans, Immunosuppressive Agents, Infant, Infant, Newborn, Islets of Langerhans, Stem Cells, Bioreactors, Stem Cell Transplantation, Pluripotent Stem Cells, Insulin-Secreting Cells, Mice, Embryonic Stem Cells
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