Viral-Mediated Gene Therapy for the Generation of Artificial Insulin-Producing Cells as a Therapeutic Treatment for Type 1 Diabetes Mellitus
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- Pancreatic Islet Biology, 2016, pp. 241 - 257
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Over the past decade, several approaches have been employed to develop cell and gene therapy strategies that generate artificial insulin-producing cells (IPCs) for potential therapeutic applications in the treatment of type 1 diabetes mellitus (T1D) . The genetic engineering of functional IPCs necessitates a broad understanding of the pancreatic developmental process and the β cell transcription factors that govern mature β cell differentiation and function. To successfully obtain functional IPCs, the type of vectors utilised for gene transfer and the selection of a suitable target cell for subsequent differentiation into IPCs is of fundamental importance. Techniques for manufacturing IPCs include the dedifferentiation and directed transdifferentiation of autologous or allogeneic cells ex vivo followed by transplantation and the in vivo transdifferentiation of target tissue via viral gene transfer. Ultimately, the goal is to construct IPCs that have the capacity to process, store and secrete insulin in response to fluctuating blood glucose levels, whilst avoiding the administration of immunosuppressants and recurrent autoimmune destruction, thereby indefinitely restoring normoglycaemia.
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