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.
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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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