Advances in Islet Transplantation and the Future of Stem Cell–Derived Islets to Treat Diabetes
Abstract
β-Cell replacement for type 1 diabetes (T1D) can restore normal glucose homeostasis, thereby eliminating the need for exogenous insulin and halting the progression of diabetes complications. Success in achieving insulin independence following transplantation of cadaveric islets fueled academic and industry efforts to develop techniques to mass produce β cells from human pluripotent stem cells, and these have now been clinically validated as an alternative source of regulated insulin production. Various encapsulation strategies are being pursued to contain implanted cells in a retrievable format, and different implant sites are being explored with some strategies reaching clinical studies. Stem cell lines, whether derived from embryonic sources or reprogrammed somatic cells, are being genetically modified for designer features, including immune evasiveness to enable implant without the use of chronic immunosuppression. Although hurdles remain in optimizing large-scale manufacturing, demonstrating efficacy, durability, and safety, products containing stem cell-derived β cells promise to provide a potent treatment for insulin-dependent diabetes.
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Embryonic stem cell-derived β-cell precursors in macroencapsulation devices implanted subcutaneously did not allow graft survival and function in the Viacyte VC-01 trial because the device biomaterial developed a foreign body reaction and nutrient diffusion was insufficient for cell survival.
“Embryonic stem cellderived βcell precursors in macroencapsulation devices implanted subcutaneously did not allow graft survival and function in the Viacyte VC01 trial because the device biomaterial developed a foreign body reaction and nutrient diffusion was insufficient for cell survival.70”
From The future of type 1 diabetes therapy (2025) · cites this paper as [70]
In the Vertex 264 phase 1 clinical trial, cells were transplanted within a proprietary encapsulation device; however, this trial did not meet its primary endpoint.
“In the Vertex 264 phase 1 clinical trial, cells were transplanted within a proprietary encapsulation device; however, this trial did not meet its primary endpoint.70”
From The future of type 1 diabetes therapy (2025) · cites this paper as [70]
When the device was modified to allow vessel entry, the cells survived, and C-peptide was measurable with an effect on glucose control and insulin requirement.
“When the device was modified to allow vessel entry, the cells survived, and Cpeptide was measurable with an effect on glucose control and insulin requirement.”
From The future of type 1 diabetes therapy (2025) · cites this paper as [70]
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References 134 · Cited by 7
- Authors
- Kieffer, T. J., Hoesli, C. A., & Shapiro, A. M. J.
- Affiliations
- University of British Columbia (CA)
- McGill University (CA)
- University of Alberta (CA)
- Venue
- Cold Spring Harbor Perspectives in Medicine
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2024-07-29
- Volume
- 15
- Issue
- 5
- Pages
- a041624
- ISSN
- 2157-1422 (ISSN-L)
- OpenAlex
- W4401075069
- Cited by
- 7
- References
- 134
- Citations by year
- 2026: 4 · 2025: 3
- Type
- posted content
- Language
- en
- Open access
- closed
- Locations
- Cold Spring Harbor Perspectives in Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Breakthrough T1D Canada (5-SRA-2021-1150-S-B, 3-COE-2022-1103-M-B)
- 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
- islet transplantation, stem cell-derived beta cells, type 1 diabetes, beta cell replacement, pluripotent stem cells, cell encapsulation, implantation site, immune evasion, genetic modification of stem cells, insulin independence
- MeSH terms
- Animals, Diabetes Mellitus, Type 1, Humans, Islets of Langerhans Transplantation, Stem Cell Transplantation, Pluripotent Stem Cells, Insulin-Secreting Cells
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