Gastrin producing syngeneic mesenchymal stem cells protect non-obese diabetic mice from type 1 diabetes
| Autor: | Marie-Claude Gaudreau, Radhika R. Gudi, Gongbo Li, Benjamin M. Johnson, Chenthamarakshan Vasu |
|---|---|
| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | Autoimmunity |
| ISSN: | 1607-842X 0891-6934 |
| DOI: | 10.1080/08916934.2021.2012165 |
| Popis: | Progressive destruction of pancreatic islet ��-cells by immune cells is a primary feature of type 1 diabetes (T1D) and therapies that can restore the functional ��-cell mass are needed to alleviate disease progression. Here, we report the use of mesenchymal stromal/stem cells (MSCs) for the production and delivery of Gastrin, a peptide hormone that is produced by intestinal cells and foetal islets and can increase ��-Cell mass, to promote protection from T1D. A single injection of syngeneic MSCs that were engineered to express Gastrin (Gastrin-MSCs) caused a significant delay in hyperglycaemia in non-obese diabetic (NOD) mice compared to engineered control-MSCs. Similar treatment of early-hyperglycaemic mice caused the restoration of euglycemia for a considerable duration, and these therapeutic effects were associated with the protection of, and/or higher frequencies of, insulin-producing islets and less severe insulitis. While the overall immune cell phenotype was not affected profoundly upon treatment using Gastrin-MSCs or upon in vitro culture, pancreatic lymph node cells from Gastrin-MSC treated mice, upon ex vivo challenge with self-antigen, showed a Th2 and Th17 bias, and diminished the diabetogenic property in NOD-Rag1 deficient mice suggesting a disease protective immune modulation under Gastrin-MSC treatment associated protection from hyperglycaemia. Overall, this study shows the potential of production and delivery of Gastrin in vivo, by MSCs, in protecting insulin-producing ��-cells and ameliorating the disease progression in T1D. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|