Stem Cell-Derived, Fully Differentiated Islets for Type 1 Diabetes.
Abstract
BACKGROUND: Zimislecel is an allogeneic stem cell-derived islet-cell therapy. Data on the safety and efficacy of zimislecel in persons with type 1 diabetes are needed. METHODS: cells) as a single infusion. All the participants also received glucocorticoid-free immunosuppressive therapy. The primary end point in part A was safety. The primary end point in part C was freedom from severe hypoglycemic events during days 90 through 365, with a glycated hemoglobin level of less than 7% or a decrease of at least 1 percentage point from baseline in the glycated hemoglobin level at one or more time points between days 180 and 365. Secondary end points in part C included safety and insulin independence between days 180 and 365. Assessment of the primary and secondary end points in part C involved the participants who received the full dose of zimislecel as a single infusion in part B or C. Detection of serum C-peptide during a 4-hour mixed-meal tolerance test was used to assess engraftment and islet function. All the analyses were interim and not prespecified. RESULTS: A total of 14 participants (2 in part A and 12 in parts B and C) completed at least 12 months of follow-up and were included in the analyses. C-peptide was undetectable at baseline in all 14 participants. After zimislecel infusion, all the participants had engraftment and islet function, as evidenced by the detection of C-peptide. Neutropenia was the most common serious adverse event, occurring in 3 participants. Two deaths occurred - one caused by cryptococcal meningitis and one by severe dementia with agitation owing to the progression of preexisting neurocognitive impairment. All 12 participants in parts B and C were free of severe hypoglycemic events and had a glycated hemoglobin level of less than 7%; these participants spent more than 70% of the time in the target glucose range (70 to 180 mg per deciliter). Ten of the 12 participants (83%) had insulin independence and were not using exogenous insulin at day 365. CONCLUSIONS: The results of this small, short-term study involving persons with type 1 diabetes support the hypothesis that zimislecel can restore physiologic islet function, warranting further clinical investigation. (Funded by Vertex Pharmaceuticals; VX-880-101 FORWARD ClinicalTrials.gov number, NCT04786262.).
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Vertex-880 is an off-the-shelf embryonic stem cell-derived product consisting of differentiated post-mitotic β cells delivered into the portal vein and protected from alloimmune and autoimmune attack by conventional immunosuppression.
“This offtheshelf embryonic stem cellderived product consists of differentiated post mitotic β cells delivered into the portal vein and protected from alloimmune and autoimmune attack by conventional immuno suppression.”
From The future of type 1 diabetes therapy (2025) · cites this paper as [71]
Vertex-880 cells were successful in a 2025 phase 1/2 trial.
“Vertex880 (Vertex Pharmaceuticals, Boston, MA, USA) cells were successful in a 2025 phase 1/2 trial.71”
From The future of type 1 diabetes therapy (2025) · cites this paper as [71]
Two deaths occurred in the Vertex-880 trial, neither of which were related to the procedure or the cells.
“Two deaths occurred, neither of which were related to the procedure or the cells.”
From The future of type 1 diabetes therapy (2025) · cites this paper as [71]
These studies indicate that current technology can produce stem-cell derived β cells capable of reversing type 1 diabetes.
“These studies indicate that current technology can produce stemcell derived β cells capable of reversing type 1 diabetes (figure 2).”
From The future of type 1 diabetes therapy (2025) · cites this paper as [71]
Although stem-cell therapy has shown remarkable results in a few people, its promise as a therapy for broad application is dependent on the safe engineering of cells that avoid both alloimmunity and autoimmunity, and on production methods that meet the global demand for cell-based therapy at affordable costs.
“Although stemcell therapy has shown remarkable results in a few people, 71,72 its promise as a therapy for broad application is dependent on the safe engineering of cells that avoid both alloimmunity and autoimmunity, and on production methods that meet the global demand for cellbased therapy at affordable costs.”
From The future of type 1 diabetes therapy (2025) · cites this paper as [71]
Cites
(1993) · New England Journal of Medicine · doi:10.1056/nejm199309303291401 · Cited by 24,667 · see citing works
Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes
(2005) · New England Journal of Medicine · doi:10.1056/nejmoa052187 · Cited by 5,138 · see citing works
Hyperglycemic crises in adult patients with diabetes
Kitabchi, A. E., Umpierrez, G. E., Miles, J. M., & Fisher, J. N. (2009) · Diabetes Care · doi:10.2337/dc09-9032 · Cited by 2,062 · see citing works
Generation of Functional Human Pancreatic β Cells In Vitro
Pagliuca, F. W., Millman, J. R., Gürtler, M., Segel, M., Van Dervort, A., Ryu, J. H., Peterson, Q. P., Greiner, D., & Melton, D. A. (2014) · Cell · doi:10.1016/j.cell.2014.09.040 · Cited by 2,025 · see citing works
Self-citationDiMeglio, L. A., Evans-Molina, C., & Oram, R. A. (2018) · The Lancet · doi:10.1016/s0140-6736(18)31320-5 · Cited by 1,561 · see citing works
Katsarou, A., Gudbjörnsdottir, S., Rawshani, A., Dabelea, D., Bonifacio, E., Anderson, B. J., Jacobsen, L. M., Schatz, D. A., & Lernmark, Å. (2017) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2017.16 · Cited by 1,475 · see citing works
Gregory, G. A., Robinson, T. I. G., Linklater, S. E., Wang, F., Colagiuri, S., de Beaufort, C., Donaghue, K. C., Harding, J. L., Wander, P. L., Zhang, X., et al. (2022) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(22)00218-2 · Cited by 1,149 · see citing works
Type 1 Diabetes Through the Life Span: A Position Statement of the American Diabetes Association
Chiang, J. L., Kirkman, M. S., Laffel, L. M., Peters, A. L., & Authors, O. B. O. T. T. 1. D. S. (2014) · Diabetes Care · doi:10.2337/dc14-1140 · Cited by 976 · see citing works
Self-citationGold, A. E., Macleod, K. M., & Frier, B. M. (1994) · Diabetes Care · doi:10.2337/diacare.17.7.697 · Cited by 810 · see citing works
The Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Study Research Group (2016) · Diabetes Care · doi:10.2337/dc15-1990 · Cited by 712 · see citing works
Holt, R. I. G., DeVries, J. H., Hess-Fischl, A., Hirsch, I. B., Kirkman, M. S., Klupa, T., Ludwig, B., Nørgaard, K., Pettus, J., Renard, E., et al. (2021) · Diabetes Care · doi:10.2337/dci21-0043 · Cited by 699 · see citing works
Self-citationType 1 diabetes mellitus as a disease of the β-cell (do not blame the immune system?)
Roep, B. O., Thomaidou, S., van Tienhoven, R., & Zaldumbide, A. (2020) · Nature Reviews Endocrinology · doi:10.1038/s41574-020-00443-4 · Cited by 646 · see citing works
Hering, B. J., Clarke, W. R., Bridges, N. D., Eggerman, T. L., Alejandro, R., Bellin, M. D., Chaloner, K., Czarniecki, C. W., Goldstein, J. S., Hunsicker, L. G., et al. (2016) · Diabetes Care · doi:10.2337/dc15-1988 · Cited by 645 · see citing works
Self-citationCharting cellular identity during human in vitro β-cell differentiation
Veres, A., Faust, A. L., Bushnell, H. L., Engquist, E. N., Kenty, J. H.-R., Harb, G., Poh, Y.-C., Sintov, E., Gürtler, M., Pagliuca, F. W., et al. (2019) · Nature · doi:10.1038/s41586-019-1168-5 · Cited by 552 · see citing works
Self-citation6. Glycemic Goals and Hypoglycemia: Standards of Care in Diabetes—2024
ElSayed, N. A., Aleppo, G., Bannuru, R. R., Bruemmer, D., Collins, B. S., Ekhlaspour, L., Hilliard, M. E., Johnson, E. L., Khunti, K., Lingvay, I., et al. (2023) · Diabetes Care · doi:10.2337/dc24-s006 · Cited by 541 · see citing works
Tamez-Pérez, H. E. (2015) · World Journal of Diabetes · doi:10.4239/wjd.v6.i8.1073 · Cited by 387 · see citing works
Hypoglycemia, functional brain failure, and brain death.
Cryer, P. E. (2007) · Journal of Clinical Investigation · doi:10.1172/jci31669 · Cited by 363 · see citing works
Bellin, M. D., Barton, F. B., Heitman, A., Harmon, J. V., Kandaswamy, R., Balamurugan, A. N., Sutherland, D. E. R., Alejandro, R., & Hering, B. J. (2012) · American Journal of Transplantation · doi:10.1111/j.1600-6143.2011.03977.x · Cited by 350 · see citing works
Choudhary, P., Rickels, M. R., Senior, P. A., Vantyghem, M.-C., Maffi, P., Kay, T. W., Keymeulen, B., Inagaki, N., Saudek, F., Lehmann, R., et al. (2015) · Diabetes Care · doi:10.2337/dc15-0090 · Cited by 233 · see citing works
Self-citationEbekozien, O. A., Mungmode, A., Sanchez, J. E., Rompicherla, S., Demeterco‐Berggren, C., Weinstock, R. S., Jacobsen, L. M., Davis, G. M., McKee, A. M., Aktürk, H. K., et al. (2023) · Diabetes Technology & Therapeutics · doi:10.1089/dia.2023.0320 · Cited by 211 · see citing works
The journey of islet cell transplantation and future development
Gamble, A., Pepper, A. R., Bruni, A., & Shapiro, A. M. J. (2018) · Islets · doi:10.1080/19382014.2018.1428511 · Cited by 171 · see citing works
State of the Art of Clinical Islet Transplantation and Novel Protocols of Immunosuppression
Shapiro, A. M. J. (2011) · Current Diabetes Reports · doi:10.1007/s11892-011-0217-8 · Cited by 153 · see citing works
Hafiz, M. M., Faradji, R., Froud, T., Pileggi, A., Baidal, D., Cure, P., Ponte, G., Poggioli, R., Cornejo, A., Messinger, S., et al. (2005) · Transplantation · doi:10.1097/01.tp.0000187881.97068.77 · Cited by 111 · see citing works
Self-citationVantyghem, M.-C., Chetboun, M., Gmyr, V., Jannin, A., Espiard, S., Le Mapihan, K., Raverdy, V., Delalleau, N., Machuron, F., Hubert, T., et al. (2019) · Diabetes Care · doi:10.2337/dc19-0401 · Cited by 105 · see citing works
Sherr, J. L., Laffel, L. M., Liu, J., Wolf, W. A., Bispham, J. A., CHAPMAN, K. S. M., Finan, D. A., Titievsky, L., Liu, T., Hagan, K. A., et al. (2024) · Diabetes Care · doi:10.2337/dc23-1765 · Cited by 104 · see citing works
Rickels, M. R., Liu, C., Shlansky-Goldberg, R. D., Soleimanpour, S. A., Vivek, K., Kamoun, M., Min, Z., Markmann, E., Palangian, M., Dalton-Bakes, C., et al. (2013) · Diabetes · doi:10.2337/db12-1802 · Cited by 103 · see citing works
Self-citationRenard, É., Ikegami, H., Vianna, A. G. D., Pozzilli, P., Brette, S., Bosnyák, Z., Lauand, F., Peters, A. L., Pilorget, V., Jurišić‐Eržen, D., et al. (2020) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.3430 · Cited by 79 · see citing works
Self-citationChanges in liver enzymes after clinical islet transplantation1
Rafael, E., Ryan, E., Paty, B., Oberholzer, J., Imes, S., Senior, P., McDonald, C., Lakey, J., & Shapiro, A. M. J. (2003) · Transplantation · doi:10.1097/01.tp.0000098822.85924.4c · Cited by 62 · see citing works
Rickels, M. R., Eggerman, T. L., Bayman, L., Qidwai, J. C., Alejandro, R., Bridges, N. D., Hering, B. J., Markmann, J. F., Senior, P. A., Hunsicker, L. G., et al. (2022) · Diabetes Care · doi:10.2337/dc21-2688 · Cited by 54 · see citing works
Self-citationAutomated Insulin Delivery: A Milestone on the Road to Insulin Independence in Type 1 Diabetes
Limbert, C., Kowalski, A. J., & Danne, T. (2024) · Diabetes Care · doi:10.2337/dci24-0007 · Cited by 16 · see citing works
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The future of type 1 diabetes therapy
Ziegler, A.-G., Cengiz, E., & Kay, T. W. H. (2025) · The Lancet · doi:10.1016/s0140-6736(25)01438-2 · Cited by 42 · see citing works
- Authors
- Reichman, T. W., Markmann, J. F., Odorico, J., Witkowski, P., Fung, J. J., Wijkstrom, M., Kandeel, F., de Koning, E. J. P., Peters, A. L., Mathieu, C., Kean, L. S., Bruinsma, B. G., Wang, C., Mascia, M., Sanna, B., Marigowda, G., Pagliuca, F., Melton, D., Ricordi, C., & Rickels, M. R.
- Affiliations
- University Health Network (CA)
- University of Pennsylvania (US)
- University of Wisconsin–Madison (US)
- University of Chicago (US)
- University of Pittsburgh Medical Center (US)
- City Of Hope National Medical Center (US)
- Leiden University Medical Center, Leiden, the Netherlands
- University of Southern California (US)
- KU Leuven (BE)
- Boston Children's Hospital (US)
- Vertex Pharmaceuticals (United States) (US)
- University of Miami (US)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2025-09-04
- Volume
- 393
- Issue
- 9
- Pages
- 858-868
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W4411474669
- Semantic Scholar
- e607e9ea81d06137d62a6fae26167f4eb44c9cb5
- Cited by
- 177
- References
- 30
- Citations by year
- 2026: 130 · 2025: 46 · 2024: 1
- FWCI
- 166.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Lirias (KU Leuven) (submittedVersion)
- Funders
- Vertex Pharmaceuticals
- Topics
- Health Sciences › Medicine › Surgery › 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, stem cell-derived islets, islet transplantation, allogeneic cell therapy, hypoglycemia, HbA1c, insulin independence, C-peptide, islet engraftment, neutropenia, mixed meal tolerance test, treatment efficacy and safety, neurocognitive impairment
- MeSH terms
- Adolescent, Adult, Blood Glucose, C-Peptide, Cell Differentiation, Diabetes Mellitus, Type 1, Female, Follow-Up Studies, Glycated Hemoglobin, Humans, Hypoglycemia, Hypoglycemic Agents, Immunosuppressive Agents, Infusions, Intravenous, Insulin, Islets of Langerhans, Male, Middle Aged, Transplantation, Homologous, Islets of Langerhans Transplantation, Young Adult
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