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Review
. 2022 Jul 8;11(14):2145.
doi: 10.3390/cells11142145.

Pancreatic Transdifferentiation Using β-Cell Transcription Factors for Type 1 Diabetes Treatment

Alexandra L G Mahoney  1 , Najah T Nassif  1 , Bronwyn A O'Brien  1 , Ann M Simpson  1
Affiliations
Review

Pancreatic Transdifferentiation Using β-Cell Transcription Factors for Type 1 Diabetes Treatment

Alexandra L G Mahoney et al. Cells. .

Abstract

Type 1 diabetes is a chronic illness in which the native beta (β)-cell population responsible for insulin release has been the subject of autoimmune destruction. This condition requires patients to frequently measure their blood glucose concentration and administer multiple daily exogenous insulin injections accordingly. Current treatments fail to effectively treat the disease without significant side effects, and this has led to the exploration of different approaches for its treatment. Gene therapy and the use of viral vectors has been explored extensively and has been successful in treating a range of diseases. The use of viral vectors to deliver β-cell transcription factors has been researched in the context of type 1 diabetes to induce the pancreatic transdifferentiation of cells to replace the β-cell population destroyed in patients. Studies have used various combinations of pancreatic and β-cell transcription factors in order to induce pancreatic transdifferentiation and have achieved varying levels of success. This review will outline why pancreatic transcription factors have been utilised and how their application can allow the development of insulin-producing cells from non β-cells and potentially act as a cure for type 1 diabetes.

Keywords: beta-cell transcription factors; gene therapy; pancreatic transdifferentiation; type 1 diabetes; viral vectors.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Representation of the hierarchy of the human pancreatic transcription factors involved in the development and differentiation of pancreatic cells. FoxA2 is present in the pancreatic buds, which develop from the endodermal layer. Pdx1 allows the development of the pancreas and differentiation of pancreatic cells through interaction with other transcription factors: Hes1 and Prox1 to non-endocrine cell lineages and Ngn3, NeuroD1 and Sox9+ to endocrine cells. Pax4 and MafA then are thought to mediate the direct differentiation to the β-cell phenotype. The α-cells, β-cells and δ-cells secrete glucagon, insulin and somatostatin, respectively. The pancreatic polypeptide cells secrete pancreatic polypeptide which regulates the secretory activity of the pancreas.
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Grants and funding

A.L.G. Mahoney was supported by an Australian Government Research Training Stipend.