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Islet transplantation in 2022

A spectacular year for islet and stem cell transplantation

Nature Reviews Endocrinology volume 19, pages 68–69 (2023)Cite this article

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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.

The Vertex trial followed closely on the heels of two ground-breaking reports3,4 from ViaCyte Inc. (owned now by Vertex), in which embryonic stem cell-derived islet progenitor cells (PEC-01) were surgically implanted within small (1.5 cm × 1 cm) devices beneath the skin. These two reports showed the implants to be safe, well tolerated and without risk of off-target growth. Insulin expression within β-cells was present in 63% of units at 3–12 months after transplantation, with a predominance of α-cells reflecting the immature state of the graft. Meal-responsive C-peptide was evident by 26 weeks3, and in the second report measurable serum levels of C-peptide were present in one-third of patients4. These results are impressive, considering the unfavourable nature of the hypoxic subcutaneous environment.

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Fig. 1: Progress in islet transplantation in 2022.

References

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Authors and Affiliations

  1. Department of Surgery, Clinical Islet Transplant Program, University of Alberta, Edmonton, Alberta, Canada

    A. M. James Shapiro & Kevin Verhoeff

  2. Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada

    A. M. James Shapiro & Kevin Verhoeff

Authors
  1. A. M. James Shapiro
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  2. Kevin Verhoeff
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Corresponding author

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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