首页|Current Status, Barriers, and Future Directions for Humanized Mouse Models to Evaluate Stem Cell-Based Islet Cell Transplant

Current Status, Barriers, and Future Directions for Humanized Mouse Models to Evaluate Stem Cell-Based Islet Cell Transplant

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Islet cell transplant (ITx) continues to improve, with recently published long-term outcomes suggesting nearly 80% graft survival, leading to improvements in glycemic control, reductions in insulin doses, and near-complete abrogation of severe hypoglycemia. Unfortunately, access to ITx remains limited by immunosuppression requirements and donor supply. Discovery of stem cell-derived functional islet-like clusters with the capacity to reverse diabetes offers a renewable, potentially immunosuppression-free solution for future widespread ITx. Evaluation and optimization of these therapies is ongoing, but may one day provide a realistic cure for type 1 diabetes. However, stem cellbased ITx has unique immunologic questions that remain unanswered. Here, we briefly synthesize current approaches for stem cell-derived ITx, review humanized mice models, and elaborate on the potential of humanized mice models for bridging the gap between current small rodent models and human clinical trials for allogeneic and autologous inducible pluripotent stem cell (iPSC)-based ITx while highlighting limitations and future directions.

DiabetesHumanized mouse modelImmunosuppressionInducible pluripotent stem cellsIslet cell transplantTransplant

Kevin Verhoeff、Braulio A. Marfil-Garza、Nerea Cuesta-Gomez、Ila Jasra、Nidheesh Dadheech、A. M. James Shapiro

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Department of Surgery, University of Alberta, Edmonton, AB, Canada

2022

Advances in Experimental Medicine and Biology

Advances in Experimental Medicine and Biology

ISSN:0065-2598
年,卷(期):2022.1387