Ayşegül AÇIKSARI, Erdal KARAÖZ, Gökhan DURUKSU

Improved insulin-secreting properties of pancreatic islet mesenchymal stem cells by constitutive expression of Pax4 and MafA

For long-term treatment of diabetes type 1, transplantation of insulin-producing beta cells may be a promising method, but thelimited number of islets for transplantation requires the development of different approaches. In this study, we aimed to generate beta- like insulin-producing cells. For this purpose, MafA, Pax4, and Ngn3 genes were transferred into pancreatic islet-derived mesenchymalstem cells, and the effect of their ectopic expressions on differentiation efficiency was examined. Stemness properties of pancreaticislet stem cells were characterized. The 3 genes were transfected by electroporation and expressed constitutively. The transfected cellswere further stimulated to differentiate by using chemical induction. Pax4 expression had significant effects on differentiation intoinsulin-producing cells. Although it caused morphological alterations in cells, similar to epithelial cells, the insulin secretion levelsremained lower than those of the cell line cotransfected with MafA and Pax4. Cotransfection of the 3 transcription factors did notfurther improve the beta-like cell generation. MafA and Pax4 ectopic expression resulted in improved differentiation efficiency intoinsulin-secreting cells. However, support of this differentiation process using additional chemical induction may suffice to overcomecontrol by endogenous regulatory pathways.

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