Insulin expression and C-peptide in type 1 diabetes subjects implanted with stem cell-derived pancreatic endoderm cells in an encapsulation device
Open accessAbstract
These preliminary data from an ongoing first-in-human phase 1/2, open-label study provide proof-of-concept that pluripotent stem cell-derived pancreatic endoderm cells (PEC-01) engrafted in type 1 diabetes patients become islet cells releasing insulin in a physiologically regulated fashion. In this study of 17 subjects aged 22-57 with type 1 diabetes, PEC-01 cells were implanted subcutaneously in VC-02 macroencapsulation devices, allowing for direct vascularization of the cells. Engraftment and insulin expression were observed in 63% of VC-02 units explanted from subjects at 3-12 months post-implant. Six of 17 subjects (35.3%) demonstrated positive C-peptide as early as 6 months post-implant. Most reported adverse events were related to surgical implant or explant procedures (27.9%) or to side-effects of immunosuppression (33.7%). Initial data suggest that pluripotent stem cells, which can be propagated to the desired biomass and differentiated into pancreatic islet-like tissue, may offer a scalable, renewable alternative to pancreatic islet transplants.
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Observed circulating C-peptide levels in these studies were too low to induce a measurable clinical benefit attributable to the transplanted cells.
“While the observed circulating C-peptide levels in these studies were too low to induce a measurable clinical benefit attributable to the transplanted cells, these clinical trials have demonstrated that facilitating host-derived vascularization into the graft promoted long-term endocrine cell survival and function in humans.”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [35]
The Discussion’s ‘Limitations of the study’ section reports measurable C-peptide but no statistically significant clinical benefit in this pilot study. It says the lack of benefit is *most likely* due to insufficient engrafted β-cell mass; the claim states more definitively that the circulating C-peptide levels were too low to cause a benefit and extends the finding to multiple studies. (LLM, conf=0.84)
Experimental — accuracy not yet measuredFacilitating host-derived vascularization into the graft promoted long-term endocrine cell survival and function in humans.
“While the observed circulating C-peptide levels in these studies were too low to induce a measurable clinical benefit attributable to the transplanted cells, these clinical trials have demonstrated that facilitating host-derived vascularization into the graft promoted long-term endocrine cell survival and function in humans.”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [35]
The Results (Histology of explanted units; page not provided) show host blood vessels entering the devices and greater vessel density in regions containing endocrine graft cells at 9–12 months. The Results also report engraftment and insulin expression through 12 months and responsive C-peptide through 24 months. These findings support long-term survival and function alongside vascularization, but do not establish that vascularization promoted them. (LLM, conf=0.84)
Experimental — accuracy not yet measuredIn the ViaCyte clinical trial, explanted grafts after months in vivo were highly heterogenous between patients because the cells were transplanted as pancreatic progenitors and allowed to finish differentiating in vivo.
“In the ViaCyte clinical trial, the explanted grafts after months in vivo were observed to be highly heterogenous between patients since the cells were transplanted as pancreatic progenitors and allowed to finish differentiating in vivo.33,35”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [35]
The Results (Histology of explanted units; page unavailable) describe explants collected 3–12 months after implantation and differences in their cellular and non-cellular regions. The Discussion says the implanted pancreatic progenitor cells differentiated and matured in vivo. Neither section establishes that differentiation caused the variation between patients; the Limitations section instead discusses variable engraftment and infiltration by host myofibroblasts. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn other regions of the device, host fibroblasts were the predominant cell type, resulting in deposition of fibrotic tissue rather than host-derived vasculature.
“In other regions of the device, however, host fibroblasts were the predominant cell type, resulting in the deposition of fibrotic tissue rather than host-derived vasculature.”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [35]
Upon graft removal, a majority of graft-derived cells immunostained for the general endocrine marker chromogranin A (CHGA).
“Upon graft removal, a majority of these graft-derived cells immunostained for the general endocrine marker chromogranin A (CHGA).”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [35]
These studies did not detect any serious safety concerns related to the transplanted cells, such as tumor formation.
“Importantly, these studies did not detect any serious safety concerns related to the transplanted cells, such as tumor formation.”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [35]
The PEC-Direct trial demonstrated glucose responsive C-peptide production 6-9 months post-transplant as the grafted cells matured from pancreatic progenitors into pancreatic endocrine cells.
“They demonstrated glucose responsive C-peptide production 6-9 months post-transplant as the grafted cells matured from pancreatic progenitors into pancreatic endocrine cells.”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [35]
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Characterization of stem-cell-derived islets during differentiation and after implantation
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Self-citation
- Authors
- Shapiro, A. M. J., Thompson, D., Donner, T. W., Bellin, M. D., Hsueh, W., Pettus, J., Wilensky, J., Daniels, M., Wang, R. M., Brandon, E. P., Jaiman, M. S., Kroon, E. J., D’Amour, K. A., & Foyt, H. L.
- Affiliations
- University of Alberta (CA)
- University of British Columbia (CA)
- Johns Hopkins University (US)
- University of Minnesota Medical Center (US)
- The Ohio State University (US)
- UC San Diego Health System (US)
- Scripps Memorial Hospital (US)
- ViaCyte (United States) (US)
- Corresponding author
- Foyt, Howard L.
- ORCID
- Venue
- Cell Reports Medicine
- Publisher
- Elsevier BV
- Published
- 2021-12
- Volume
- 2
- Issue
- 12
- Pages
- 100466
- ISSN
- 2666-3791 (ISSN-L)
- PMC
- PMC8714853
- OpenAlex
- W3214819015
- Cited by
- 313
- References
- 2
- Citations by year
- 2026: 41 · 2025: 64 · 2024: 85 · 2023: 58 · 2022: 61 · 2021: 3 · 2012: 1
- FWCI
- 47.85
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports Medicine (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Stem Cell Network
- California Institute for Regenerative Medicine (CLIN2-09672)
- Juvenile Diabetes Research Foundation United States of America
- 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
- type 1 diabetes, macroencapsulation, insulin gene expression, C-peptide, cell engraftment, pluripotent stem cells
- MeSH terms
- Adolescent, Adult, Aged, C-Peptide, Diabetes Mellitus, Type 1, Endoderm, Female, Humans, Insulin, Male, Middle Aged, Pancreas, Stem Cells, Cells, Immobilized, Stem Cell Transplantation, Young Adult
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