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

Autor: Verhoeff K; Department of Surgery, University of Alberta, Edmonton, AB, Canada., Marfil-Garza BA; Department of Surgery, University of Alberta, Edmonton, AB, Canada.; National Institute of Medical Sciences and Nutrition Salvador Zubiran, Mexico City, Mexico.; CHRISTUS-LatAm Hub - Excellence and Innovation Center, Monterrey, Mexico., Cuesta-Gomez N; Alberta Diabetes Institute, University of Alberta, Edmonton, AB, Canada., Jasra I; Alberta Diabetes Institute, University of Alberta, Edmonton, AB, Canada., Dadheech N; Alberta Diabetes Institute, University of Alberta, Edmonton, AB, Canada., Shapiro AMJ; Alberta Diabetes Institute, University of Alberta, Edmonton, AB, Canada. jshapiro@ualberta.ca.; Department of Surgery and Clinical Islet Transplant Programme, University of Alberta, Edmonton, AB, Canada. jshapiro@ualberta.ca.; Li Ka Shing Centre for Health Research Innovation, Edmonton, AB, Canada. jshapiro@ualberta.ca.
Jazyk: angličtina
Zdroj: Advances in experimental medicine and biology [Adv Exp Med Biol] 2022; Vol. 1387, pp. 89-106.
DOI: 10.1007/5584_2022_711
Abstrakt: 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 cell-based 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.
(© 2022. Springer Nature Switzerland AG.)
Databáze: MEDLINE