Gastrin producing syngeneic mesenchymal stem cells protect non-obese diabetic mice from type 1 diabetes
Progressive destruction of pancreatic islet β-cells by immune cells is a primary feature of type 1 diabetes (T1D) and therapies that can restore the functional β-cell mass are needed to alleviate disease progression. Here, we report the use of mesenchymal stromal/stem cells (MSCs) for the production...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-02-01
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| Series: | Autoimmunity |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/08916934.2021.2012165 |
| _version_ | 1797684617056092160 |
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| author | Marie-Claude Gaudreau Radhika R. Gudi Gongbo Li Benjamin M. Johnson Chenthamarakshan Vasu |
| author_facet | Marie-Claude Gaudreau Radhika R. Gudi Gongbo Li Benjamin M. Johnson Chenthamarakshan Vasu |
| author_sort | Marie-Claude Gaudreau |
| collection | DOAJ |
| description | Progressive destruction of pancreatic islet β-cells by immune cells is a primary feature of type 1 diabetes (T1D) and therapies that can restore the functional β-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 β-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 β-cells and ameliorating the disease progression in T1D. |
| first_indexed | 2024-03-12T00:32:20Z |
| format | Article |
| id | doaj.art-9442f32867934e96bd9e6b799329d242 |
| institution | Directory Open Access Journal |
| issn | 0891-6934 1607-842X |
| language | English |
| last_indexed | 2024-03-12T00:32:20Z |
| publishDate | 2022-02-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Autoimmunity |
| spelling | doaj.art-9442f32867934e96bd9e6b799329d2422023-09-15T10:12:24ZengTaylor & Francis GroupAutoimmunity0891-69341607-842X2022-02-015529510810.1080/08916934.2021.20121652012165Gastrin producing syngeneic mesenchymal stem cells protect non-obese diabetic mice from type 1 diabetesMarie-Claude Gaudreau0Radhika R. Gudi1Gongbo Li2Benjamin M. Johnson3Chenthamarakshan Vasu4Department of Microbiology and Immunology, College of Medicine, Medical University of South CarolinaDepartment of Microbiology and Immunology, College of Medicine, Medical University of South CarolinaDepartment of Surgery, University of Illinois at ChicagoDepartment of Microbiology and Immunology, College of Medicine, Medical University of South CarolinaDepartment of Microbiology and Immunology, College of Medicine, Medical University of South CarolinaProgressive destruction of pancreatic islet β-cells by immune cells is a primary feature of type 1 diabetes (T1D) and therapies that can restore the functional β-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 β-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 β-cells and ameliorating the disease progression in T1D.http://dx.doi.org/10.1080/08916934.2021.2012165mesenchymal stem cellstype 1 diabetesgastrinautoimmunityinsulitisimmune modulation |
| spellingShingle | Marie-Claude Gaudreau Radhika R. Gudi Gongbo Li Benjamin M. Johnson Chenthamarakshan Vasu Gastrin producing syngeneic mesenchymal stem cells protect non-obese diabetic mice from type 1 diabetes Autoimmunity mesenchymal stem cells type 1 diabetes gastrin autoimmunity insulitis immune modulation |
| title | Gastrin producing syngeneic mesenchymal stem cells protect non-obese diabetic mice from type 1 diabetes |
| title_full | Gastrin producing syngeneic mesenchymal stem cells protect non-obese diabetic mice from type 1 diabetes |
| title_fullStr | Gastrin producing syngeneic mesenchymal stem cells protect non-obese diabetic mice from type 1 diabetes |
| title_full_unstemmed | Gastrin producing syngeneic mesenchymal stem cells protect non-obese diabetic mice from type 1 diabetes |
| title_short | Gastrin producing syngeneic mesenchymal stem cells protect non-obese diabetic mice from type 1 diabetes |
| title_sort | gastrin producing syngeneic mesenchymal stem cells protect non obese diabetic mice from type 1 diabetes |
| topic | mesenchymal stem cells type 1 diabetes gastrin autoimmunity insulitis immune modulation |
| url | http://dx.doi.org/10.1080/08916934.2021.2012165 |
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