Cryopreservation of Stem Cell-Derived β-Like Cells Enriches for Insulin-Producing Cells With Improved Function.
| Autor: | Barra JM; Diabetes Institute, University of Florida, Gainesville, FL., Kratz AT; Diabetes Institute, University of Florida, Gainesville, FL., Castro-Gutierrez R; Diabetes Institute, University of Florida, Gainesville, FL., Proia J; Diabetes Institute, University of Florida, Gainesville, FL., Bhardwaj G; Diabetes Institute, University of Florida, Gainesville, FL., Phelps EA; J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL., Russ HA; Diabetes Institute, University of Florida, Gainesville, FL. |
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| Jazyk: | angličtina |
| Zdroj: | Diabetes [Diabetes] 2024 Oct 01; Vol. 73 (10), pp. 1687-1696. |
| DOI: | 10.2337/db24-0346 |
| Abstrakt: | The generation of stem cell-derived β-like cells (sBCs) holds promise as not only an abundant insulin-producing cell source for replacement therapy of type 1 diabetes (T1D) but also as an invaluable model system for investigating human β-cell development, immunogenicity, and function. Several groups have developed methodology to direct differentiate human pluripotent stem cells into pancreatic cell populations that include glucose-responsive sBCs. Nevertheless, the process of generating sBCs poses substantial experimental challenges. It involves lengthy differentiation periods, there is substantial variability in efficiency, and there are inconsistencies in obtaining functional sBCs. Here, we describe a simple and effective cryopreservation approach for sBC cultures that yields homogeneous sBC clusters that are enriched for insulin-expressing cells while simultaneously depleting proliferative progenitors. Thawed sBCs have enhanced glucose-stimulated insulin release compared with controls in vitro and can effectively engraft and function in vivo. Collectively, this approach alleviates current challenges with inefficient and variable sBC generation while improving their functional state. We anticipate that these findings can inform ongoing clinical application of sBCs for the treatment of patients with T1D and serve as an important resource for the wider diabetes field that will allow for accelerated research discoveries. (© 2024 by the American Diabetes Association.) |
| Databáze: | MEDLINE |
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