Non-viral Direct Cell Reprogramming Methods Aiming to Rescue Glycemic Control in Type 1 Diabetes
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Date
2024-05
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The Ohio State University
Abstract
Allogenic islet transplantation is the current gold standard cell therapy to treat patients with severe type I diabetes. However, its implementation is limited due to a lack of donor tissue, its invasive nature, and the requirement for patients to take immunosuppressants for the remainder of their lives following treatment. To address these limitations, we primarily investigated a novel method to directly reprogram fibroblasts into induced β cells. We delivered plasmid DNA encoding for a unique combination of three skin plasticity and seven β cell patterning transcription factors (3SP+7βC) to dermal fibroblasts and skin tissue using bulk electroporation (in vitro), nanoelectroporation (in vitro), or tissue nanotransfection (in vivo). Mouse embryonic fibroblasts transfected with the 3SP+7βC combination demonstrated increased insulin 1 and insulin 2 gene expression by day 14 compared to control. Moreover, these populations of mouse embryonic fibroblasts transfected with the 3SP+7βC combination stained positive for the insulin protein. In vivo studies suggest upregulated insulin gene expression, as well as acute glycemic control rescue, and are currently ongoing. Further experiments are still needed to explore the extent of induced β cell reprogramming and the glycemic control that can be driven by the delivery of unique transcription factors using electroporation-based methods. However, this study explores a step towards providing an alternative cell source to treat, and potentially cure, the lack of insulin causing homeostatic glucose imbalance in type I diabetes. Success here has potential to greatly improve diabetic patients' quality of life and relieve the financial burden faced by patients as they monitor type I diabetes throughout their lives. These improvements would also lower the financial burden faced by healthcare systems due to decreased demands for type 1 diabetes related micro-, and macrovascular disease treatments.
Description
Travel Awardee: College of Medicine Trainee Research Day (April 2024)
Travel Awardee: Preventative Health of Adipose Tissue Symposium (April 2024)
1st place poster presentation: Engineering in Healthcare Symposium (January 2024)
1st place overall 3-Minute Thesis: College of Medicine Annual Education Symposium (January 2024)
Audience choice 3-Minute Thesis: College of Medicine Annual Education Symposium (January 2024)
Honorable Mention: BMES Engineering Endocrine Tissue (October 2023)
Travel Awardee: Preventative Health of Adipose Tissue Symposium (April 2024)
1st place poster presentation: Engineering in Healthcare Symposium (January 2024)
1st place overall 3-Minute Thesis: College of Medicine Annual Education Symposium (January 2024)
Audience choice 3-Minute Thesis: College of Medicine Annual Education Symposium (January 2024)
Honorable Mention: BMES Engineering Endocrine Tissue (October 2023)
Keywords
Type 1 Diabetes, Non-viral Cell Reprogramming, Gene and Cell Therapy, β Cell Replacement, Insulin Therapy