Development of insulin-producing cells from primitive biologic precursors
Open accessAbstract
PURPOSE OF REVIEW: The differentiation of pluripotent and multipotent stem cells into insulin-producing cells has the potential to create a renewable supply of replacement beta cells with tremendous utility in the treatment of diabetes. The purpose of this review is to summarize recent advancements in the field, with emphasis on the limitations of this technology as it relates to the beta cell. RECENT FINDINGS: Multiple groups have developed successful in-vitro protocols to differentiate human embryonic stem cells and selected tissue specific stem cells into progenitors capable of insulin production and glucose-stimulated insulin secretion. The resulting cells are immature beta cell-like cells that coexpress multiple islet hormones and lack the full complement of genes necessary for normal function. Protocols that include in-vivo maturation in immune-compromised mice produce cells with a more mature phenotype. SUMMARY: Although tremendous progress has been made in differentiating stem cells into insulin-producing cells, there is still more research needed to produce a fully functional adult beta cell.
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There has been a steady series of improvements to directed differentiation strategies for generating beta-like cells over the past 20 years.
“there has been a steady series of improvements to directed differentiation strategies over the past 20 years135–138.”
From 100 years of insulin: celebrating the past, present and future of diabetes therapy (2021) · cites this paper as [138]
The “Human embryonic stem cells as precursors” section (page not provided) describes increasingly sophisticated differentiation methods for generating insulin-producing cells. The paper was published in 2009 and discusses progress over the preceding several years; it does not establish a steady series of improvements over 20 years. (LLM, conf=0.86)
Experimental — accuracy not yet measuredA beta-like cell with behavior that fully recapitulates the physiology of a normal beta cell is yet to be realized.
“While a beta-like cell with behavior that fully recapitulates the physiology of a normal beta cell is yet to be realized”
From 100 years of insulin: celebrating the past, present and future of diabetes therapy (2021) · cites this paper as [138]
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Cites
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100 years of insulin: celebrating the past, present and future of diabetes therapy
Sims, E. K., Carr, A. L. J., Oram, R. A., DiMeglio, L. A., & Evans-Molina, C. (2021) · Nature Medicine · doi:10.1038/s41591-021-01418-2 · Cited by 270 · see citing works
Self-citation
- Authors
- Evans-Molina, C., Vestermark, G. L., & Mirmira, R. G.
- Affiliations
- Indiana University Indianapolis (US)
- Corresponding author
- Mirmira, Raghavendra G
- Venue
- Current Opinion in Organ Transplantation
- Published
- 2009-02
- Volume
- 14
- Issue
- 1
- Pages
- 56-63
- ISSN
- 1087-2418 (ISSN-L)
- PMC
- PMC3617583
- OpenAlex
- W2024357672
- Cited by
- 18
- References
- 4
- Citations by year
- 2021: 2 · 2019: 1 · 2018: 1 · 2017: 1 · 2016: 1 · 2015: 2 · 2012: 2
- FWCI
- 0.53
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Current Opinion in Organ Transplantation (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK60581, K08DK080225, R01DK060581)
- 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
- insulin-producing cells, beta cell differentiation, human embryonic stem cells, glucose-stimulated insulin secretion, in vivo maturation, islet hormones, diabetes mellitus, beta cell replacement therapy, multipotent stem cells
- MeSH terms
- Adult, Animals, Cell Differentiation, Diabetes Mellitus, Type 1, Glucose, Humans, Insulin, Stem Cells, Islets of Langerhans Transplantation, Cell Culture Techniques, Stem Cell Transplantation, Multipotent Stem Cells, Pluripotent Stem Cells, Regenerative Medicine, Cell Proliferation, Insulin-Secreting Cells, Mice, Embryonic Stem Cells
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