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  • Year in Review
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Islet transplantation in 2022

A spectacular year for islet and stem cell transplantation

The year 2022 has been notable for game-changing early progress in clinical trials with stem cell islets; durable and promising 20-year data with long-term outcomes in clinical islet transplantation; and the development of locally protective or gene-editing-based approaches to avoid long-term immunosuppression.

Key advances

  • ViaCyte Inc.’s PEC-01 trials with subcutaneous implantation of embryonic stem cell islets (SCIs) resulted in islet survival and detectable levels of C-peptide in peripheral blood; full immunosuppression was needed3.

  • Durable 20-year outcomes with human intraportal islet transplantation with sustained metabolic response were reported; full immunosuppression was needed5.

  • Islets were cotransplanted with protective mesenchymal stem cells that secreted CTLA4 and PDL1 in mice, leading to sustained allograft survival without immunosuppression7.

  • Detailed characterizations of the functional properties of mature SCIs were carried out, benchmarked against human islets, highlighting the need for thorough characterization to ensure future clinical product safety8.

  • A mixed lymphocyte response was used to target chemokine ligand 10 (CXCL10) pathways that prevent immune activation as a screening tool for CRISPR gene-editing targets10.

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Fig. 1: Progress in islet transplantation in 2022.

References

  1. Kolata, G. A. Cure for type 1 diabetes? For one man, it seems to have worked. The New York Times https://www.nytimes.com/2021/11/27/health/diabetes-cure-stem-cells.html (2021).

  2. Banting, F. G., Best, C. H., Collip, J. B., Campbell, W. R. & Fletcher, A. A. Pancreatic extracts in the treatment of diabetes mellitus. CMAJ 12, 141–146 (1922).

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  3. Ramzy, A. et al. Implanted pluripotent stem-cell-derived pancreatic endoderm cells secrete glucose-responsive C-peptide in patients with type 1 diabetes. Cell Stem Cell 28, 2047–2061.e5 (2021).

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  5. Marfil-Garza, B. A. et al. Pancreatic islet transplantation in type 1 diabetes: 20-year experience from a single-centre cohort in Canada. Lancet Diabetes Endocrinol. 10, 519–532 (2022).

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  6. Hering, B. J. et al. Factors associated with favourable 5 year outcomes in islet transplant alone recipients with type 1 diabetes complicated by severe hypoglycaemia in the Collaborative Islet Transplant Registry. Diabetologia https://doi.org/10.1007/s00125-022-05804-4 (2022).

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  7. Wang, X. et al. Engineered immunomodulatory accessory cells improve experimental allogeneic islet transplantation without immunosuppression. Sci. Adv. 8, eabn0071 (2022).

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  8. Balboa, D. et al. Functional, metabolic and transcriptional maturation of human pancreatic islets derived from stem cells. Nat. Biotechnol. 40, 1042–1055 (2022).

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  9. Sluch, V. M. et al. CRISPR-editing of hESC’s allows for production of immune evasive cells capable of differentiation to pancreatic progenitors for future type 1 diabetes therapy. Diabetologia https://www.ipscell.com/wp-content/uploads/2019/09/ViaCyte-CRISPR-EASD-Abstract-September-2019.pdf (2019).

  10. Sintov, E. et al. Whole-genome CRISPR screening identifies genetic manipulations to reduce immune rejection of stem cell-derived islets. Stem Cell Reports 17, 1976–1990 (2022).

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Correspondence to A. M. James Shapiro.

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Competing interests

A.M.J.S. holds a Canada Research Chair in Regenerative Medicine and Transplantation Surgery, and receives funding from the Canadian Stem Cell Network, the Juvenile Diabetes Research Foundation, the Diabetes Research Institute Foundation of Canada and the University Hospital Foundation. He consults for ViaCyte Inc., Protokinetix Inc., Hemostemix Inc. and Aspect Biosystems Ltd. K.V. declares no competing interests.

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Shapiro, A.M.J., Verhoeff, K. A spectacular year for islet and stem cell transplantation. Nat Rev Endocrinol 19, 68–69 (2023). https://doi.org/10.1038/s41574-022-00790-4

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