The microenvironment is an important factor of stem cells regulating their maintenance, survival, and differentiation. The glycation of proteins with reducing sugars through nonenzymatic reactions induces the collagen cross-linking, which causes tissue stiffening, which is enhanced during aging and diabetes. In this study, we aimed to analyze the effect of glycated collagen on the stem cell culture and differentiation. The collagen type 1 was modified by glycation with mannose, rhamnose, arabinose, and glucose. After the culture of mesenchymal stem cells on the coated surfaces with glycated collagen, the differences in cell adhesion, proliferation, and differentiation were compared. The results showed that the modifications did not induce apoptosis or cause cell death. However, the culture of cells on modified collagens improved the proliferation. It was found that the mannose-modified collagen stimulated the adipogenic differentiation of stem cells, and rhamnose-modified collagen supports the differentiation into both osteogenic and insulin-producing cells. The low concentration of monosaccharides during glycation process improved the characteristics of the matrix protein in favor of stem cell differentiation. Modification of the collagen by glycation might be used as a tool to improve natural polymers for material-induced stem cell differentiation in the future.

For long-term treatment of diabetes type 1, transplantation of insulin-producing beta cells may be a promising method, but the limited number of islets for transplantation requires the development of different approaches. In this study, we aimed to generate betalike insulin-producing cells. For this purpose, MafA, Pax4, and Ngn3 genes were transferred into pancreatic islet-derived mesenchymal stem cells, and the effect of their ectopic expressions on differentiation efficiency was examined. Stemness properties of pancreatic islet stem cells were characterized. The 3 genes were transfected by electroporation and expressed constitutively. The transfected cells were further stimulated to differentiate by using chemical induction. Pax4 expression had significant effects on differentiation into insulin-producing cells. Although it caused morphological alterations in cells, similar to epithelial cells, the insulin secretion levels remained lower than those of the cell line cotransfected with MafA and Pax4. Cotransfection of the 3 transcription factors did not further improve the beta-like cell generation. MafA and Pax4 ectopic expression resulted in improved differentiation efficiency into insulin-secreting cells. However, support of this differentiation process using additional chemical induction may suffice to overcome control by endogenous regulatory pathways.

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