Long-term glycemic control using polymer-encapsulated human stem cell–derived beta cells in immune-competent mice
Open accessAbstract
The transplantation of glucose-responsive, insulin-producing cells offers the potential for restoring glycemic control in individuals with diabetes. Pancreas transplantation and the infusion of cadaveric islets are currently implemented clinically, but these approaches are limited by the adverse effects of immunosuppressive therapy over the lifetime of the recipient and the limited supply of donor tissue. The latter concern may be addressed by recently described glucose-responsive mature beta cells that are derived from human embryonic stem cells (referred to as SC-β cells), which may represent an unlimited source of human cells for pancreas replacement therapy. Strategies to address the immunosuppression concerns include immunoisolation of insulin-producing cells with porous biomaterials that function as an immune barrier. However, clinical implementation has been challenging because of host immune responses to the implant materials. Here we report the first long-term glycemic correction of a diabetic, immunocompetent animal model using human SC-β cells. SC-β cells were encapsulated with alginate derivatives capable of mitigating foreign-body responses in vivo and implanted into the intraperitoneal space of C57BL/6J mice treated with streptozotocin, which is an animal model for chemically induced type 1 diabetes. These implants induced glycemic correction without any immunosuppression until their removal at 174 d after implantation. Human C-peptide concentrations and in vivo glucose responsiveness demonstrated therapeutically relevant glycemic control. Implants retrieved after 174 d contained viable insulin-producing cells.
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Transplantation of SC-islets into mice improves their insulin secretion and glucose responsiveness, suggesting that SC-islet immaturity can be resolved.
“Transplantation of SC-islets into mice improves their insulin secretion and glucose responsiveness, suggesting that SC-islet immaturity can be resolved.”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [41]
The Abstract reports human C-peptide secretion and glucose responsiveness after SC-β-cell transplantation into diabetic mice. But it describes the cells as mature and glucose-responsive before transplantation, and says they maintained their differentiation state afterward. It does not show that transplantation improved their function or resolved immaturity. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThese SC-β cells have been shown to improve glycemic control in diabetic mice.
“These cells have been shown to improve glycemic control in diabetic mice, highlighting their potential utility in vivo.36,37,39–44”
From Developments in stem cell-derived islet replacement therapy for treating type 1 diabetes (2023) · cites this paper as [41]
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References 36 · Cited by 710
Research works printed but not linked: 28
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- Authors
- Vegas, A. J., Veiseh, O., Gürtler, M., Millman, J. R., Pagliuca, F. W., Bader, A. R., Doloff, J. C., Li, J., Chen, M., Olejnik, K., Tam, H. H., Jhunjhunwala, S., Langan, E., Aresta-Dasilva, S., Gandham, S., McGarrigle, J. J., Bochenek, M. A., Hollister-Lock, J., Oberholzer, J., Greiner, D. L., Weir, G. C., Melton, D. A., Langer, R., & Anderson, D. G.
- Affiliations
- Boston Children's Hospital (US)
- Harvard University (US)
- University of Illinois Chicago (US)
- University of Massachusetts Chan Medical School (US)
- Joslin Diabetes Center (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Anderson, Daniel G
- ORCID
- Venue
- Nature Medicine
- Published
- 2016-01-25
- Volume
- 22
- Issue
- 3
- Pages
- 306-311
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC4825868
- OpenAlex
- W2265806176
- Cited by
- 710
- References
- 36
- Citations by year
- 2026: 52 · 2025: 40 · 2024: 39 · 2023: 60 · 2022: 64 · 2021: 77 · 2020: 91 · 2019: 73 · 2018: 81 · 2017: 77 · 2016: 56
- FWCI
- 105.98
- Type
- journal article
- Language
- en
- Update notices
- erratum (2016-04-06)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- PMC
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (4r37eb000244-34, 1uc4dk104218-01)
- National Cancer Institute (U54CA151884, CA151884)
- National Institute of Diabetes and Digestive and Kidney Diseases (UC4-DK-104218, P30DK036836)
- National Institute of Biomedical Imaging and Bioengineering (EB-000244, R01EB000244, R37-EB000244, EB 000351, R01EB000351)
- National Institute of Dental and Craniofacial Research (DE013023, R01DE013023)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- stem cell-derived beta cells, human embryonic stem cells, beta cell transplantation, alginate encapsulation, immunoisolation, type 1 diabetes, streptozotocin-induced diabetes, glucose-dependent insulin secretion, C-peptide, foreign body reaction, immunocompetent mice, xenotransplantation
- MeSH terms
- Alginates, Animals, Blood Glucose, C-Peptide, Cell Differentiation, Chromatography, Liquid, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 1, Disease Models, Animal, Flow Cytometry, Fluorescent Antibody Technique, Foreign-Body Reaction, Humans, Immunocompetence, Insulin, Microscopy, Phase-Contrast, Morpholines, Polymers, Triazoles, Blotting, Western, Cell Transplantation, Microscopy, Confocal, Cell Culture Techniques, Hydrogels, Insulin-Secreting Cells, Mice, Embryonic Stem Cells, Tandem Mass Spectrometry
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