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Harnessing cellular therapeutics for type 1 diabetes mellitus: progress, challenges, and the road ahead
Open accessAbstract
Type 1 diabetes mellitus (T1DM) is a growing global health concern that affects approximately 8.5 million individuals worldwide. T1DM is characterized by an autoimmune destruction of pancreatic β cells, leading to a disruption in glucose homeostasis. Therapeutic intervention for T1DM requires a complex regimen of glycaemic monitoring and the administration of exogenous insulin to regulate blood glucose levels. Advances in continuous glucose monitoring and algorithm-driven insulin delivery devices have improved the quality of life of patients. Despite this, mimicking islet function and complex physiological feedback remains challenging. Pancreatic islet transplantation represents a potential functional cure for T1DM but is hindered by donor scarcity, variability in harvested cells, aggressive immunosuppressive regimens and suboptimal clinical outcomes. Current research is directed towards generating alternative cell sources, improving transplantation methods, and enhancing cell survival without chronic immunosuppression. This Review maps the progress in cell replacement therapies for T1DM and outlines the remaining challenges and future directions. We explore the state-of-the-art strategies for generating replenishable β cells, cell delivery technologies and local targeted immune modulation. Finally, we highlight relevant animal models and the regulatory aspects for advancing these technologies towards clinical deployment.
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“One approach is to use encapsulation within devices that exclude immune cells from direct interaction with transplanted cells, 73 which is a bioengineering challenge for which high oxygen tension is required.”
From The future of type 1 diabetes therapy (2025) · cites this paper as [73]
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Self-citationEmerging Therapies in Diabetes: New Drugs and Innovative Remedies
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Metadata
- Authors
- Grattoni, A., Korbutt, G., Tomei, A. A., García, A. J., Pepper, A. R., Stabler, C., Brehm, M., Papas, K., Citro, A., Shirwan, H., Millman, J. R., Melero-Martin, J., Graham, M., Sefton, M., Ma, M., Kenyon, N., Veiseh, O., Desai, T. A., Nostro, M. C., Marinac, M., Sykes, M., Russ, H. A., Odorico, J., Tang, Q., Ricordi, C., Latres, E., Mamrak, N. E., Giraldo, J., Poznansky, M. C., & de Vos, P.
- Affiliations
- Houston Methodist (US)
- University of Alberta (CA)
- University of Miami (US)
- University of Florida (US)
- University of Massachusetts Chan Medical School (US)
- University of Arizona (US)
- IRCCS Ospedale San Raffaele (IT)
- University of Missouri (US)
- Washington University in St. Louis (US)
- University of Minnesota (US)
- University of Toronto (CA)
- Cornell University (US)
- University of California, San Francisco (US)
- University Health Network (CA)
- Breakthrough T1D (US)
- Columbia University (US)
- University of Wisconsin–Madison (US)
- Harvard University (US)
- University Medical Center Groningen (NL)
- Corresponding author
- Grattoni, Alessandro
- Giraldo, Jaime
- Poznansky, Mark C.
- de Vos, Paul
- ORCID
- Grattoni, Alessandro
- Korbutt, Gregory
- Tomei, Alice A.
- García, Andrés J.
- Pepper, Andrew R.
- Stabler, Cherie
- Brehm, Michael
- Papas, Klearchos
- Citro, Antonio
- Shirwan, Haval
- Millman, Jeffrey R.
- Melero-Martin, Juan
- Graham, Melanie
- Sefton, Michael
- Ma, Minglin
- Kenyon, Norma
- Veiseh, Omid
- Desai, Tejal A.
- Nostro, M. Cristina
- Marinac, Marjana
- Sykes, Megan
- Russ, Holger A.
- Odorico, Jon
- Tang, Qizhi
- Ricordi, Camillo
- Latres, Esther
- Mamrak, Nicholas E.
- Giraldo, Jaime
- Poznansky, Mark C.
- de Vos, Paul
- Venue
- Nature Reviews Endocrinology
- Published
- 2024-09-03
- Volume
- 21
- Issue
- 1
- Pages
- 14-30
- ISSN
- 1759-5029 (ISSN-L)
- 1759-5037
- PMC
- PMC11938328
- OpenAlex
- W4402197225
- Cited by
- 92
- References
- 227
- Citations by year
- 2026: 42 · 2025: 47 · 2024: 3
- FWCI
- 10.20
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature Reviews Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Funders
- Edward Mallinckrodt, Jr. Foundation
- Diabetes Research Connection
- Canada Research Chairs
- Ministero della Salute (2018-)
- National Institutes of Health (SCR_014393, 1uc4dk104218-01)
- National Institute of Diabetes and Digestive and Kidney Diseases (UC4-DK-104218, R01DK120444, UC24 DK104162, SCR_014393, U01DK104218, DK104162, R01 DK12044, R01DK132104, U24DK104162, R01DK114233, R01DK133610, R01DK133702, R01DK128840, R01DK132387)
- National Institute of Neurological Disorders and Stroke (R01NS122911)
- Breakthrough T1D Canada (5-CDA-2020-945-A-N, 2-SRA-2021-1079-S-B, 1-SRA-2022-1229-S-B, 5-SRA-2020-1058-S-B)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- type 1 diabetes, islet transplantation, cell therapy, beta cell regeneration, immunosuppression, continuous glucose monitoring, insulin delivery devices, animal models of diabetes, regulatory approval
- MeSH terms
- Animals, Diabetes Mellitus, Type 1, Humans, Islets of Langerhans Transplantation, Insulin-Secreting Cells, Cell- and Tissue-Based Therapy
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