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- Title
Ectopic expression of insulin in a type 1 diabetic rat model by injection of manipulated mesenchymal stem cells with an insulin construct driven by a glucose‐sensitive promoter in the port vein.
- Authors
Mohammad Dezashibi, Hoda; Farzad‐Mohajeri, Saeed; Bandehpour, Mojgan; Shabani, Aliakbar; Kazemi, Bahram
- Abstract
The treatment of type 1 diabetes through islet cell transplantation is a complex process, facing challenges such as allograft rejections and a limited supply of donors. One potential solution is to utilize the liver as an alternative for natural insulin production, as hepatocytes can secrete proteins and respond to glucose levels. Recent research has shown promising results in using mesenchymal stem cells as a potential cure for diabetes. The study utilized a diabetic rat model, confirmed through blood sugar measurement. A plasmid vector was designed with specific genetic components, synthesized by biotech company, and then Inserted vector into a plasmid with resistance genes and bacterial origin. Bone marrow‐derived mesenchymal stem cells (BM‐MSCs) were cultured and transfected with the plasmid using Lipofectamine 3000. Polymerase chain reaction was employed to confirm successful transfection using specific primers. For the animal study, 30 male Wistar rats were divided into six groups, each comprising five rats. The control group did not receive any treatment, while the second group received MSCs via Portal Vein Injection. The third group received MSCs transfected with a specific construct via Portal Vein Injection. The fourth group was induced to develop diabetes through streptozotocin (STZ) injection, the fifth group developed diabetes and received untransfected MSCs via Portal Vein Injection, and the sixth group received MSCs transfected with the specific construct via Portal Vein Injection. To manage Pain, appropriate pain control was administered to the rats for 3 days after the surgery. Fixed liver tissues obtained from the euthanized rats were utilized for immunohistochemistry. In this study, immunohistochemical techniques were used to examine insulin expression in different groups of rats. The control groups showed high levels of insulin expression, while the diabetic groups exhibited lower expression. However, there was a significant difference between the diabetic groups treated with MSC and transgenic MSC cells. All groups had similar baseline glucose levels, but the diabetic groups showed a significant increase after STZ injection, whereas the control and MSC groups did not. Postintervention, both the control and MSC groups had similar glucose levels to the post‐STZ levels. However, diabetes‐induced groups experienced a significant decrease in glucose levels, with the transfected MSCs showing a greater decrease than the untransfected MSCs. The study suggested that treatment with MSCs, especially transfected ones, can effectively reduce glucose levels in rats with diabetes. In this research, rat BM‐MSCs were utilized to create insulin‐producing mesenchymal cells with glucose‐sensitive insulin expression. The cells were transferred to the liver of diabetic rats via portal vein injection, leading to an increase in insulin expression. This study proposes a novel approach for cell therapy and delivery in the treatment of type 1 diabetes. Significance Statement: Type 1 diabetes arises from autoimmune destruction of pancreatic β cells, leading to insulin deficiency. Cell therapy, presents a promising avenue. cells can be genetically engineered to produce insulin in response to glucose fluctuations. Mesenchymal stem cells are potential candidates for generating insulin‐producing cells. This study employed a novel approach, genetically engineered using a plasmid vector with glucose‐responsive elements in bone marrow‐derived mesenchymal stem cells and cell transfer to rat liver through portal vein injection. Differing from conventional methodologies, this research utilized undifferentiated rat BM‐MSCs. The hypothesis revolved around the potential of rat BM‐MSCs to migrate into the rat liver via the Portal Vein Injection method, offering a distinctive perspective on diabetes treatment.
- Subjects
MESENCHYMAL stem cells; TYPE 1 diabetes; BLOOD sugar measurement; ANIMAL disease models; PORTAL vein; GENE transfection
- Publication
Cell Biochemistry & Function, 2023, Vol 41, Issue 8, p1412
- ISSN
0263-6484
- Publication type
Article
- DOI
10.1002/cbf.3876