Evaluation of Pancreatic Cell Proliferation and Transdifferentiation Induced by Synthetic Matrix Implantation in Insulin-Treated Diabetic Mice

The plasticity of a cell is determined by its ability to change, considering its entire epigenome, and adopt the characteristics and functions of other cells. Understanding the plasticity of pancreatic cells is currently of great clinical relevance, given the need for treatments for diseases such as diabetes and pancreatitis. It is known that the adult pancreas has a very limited capacity for regeneration; however, many studies have demonstrated that pancreatic cells can directly transdifferentiate into another cell type within the same lineage or even a different lineage. The models currently used to induce these regenerative processes with subsequent proliferation typically involve stimuli through surgical, chemical, or specific genetic interventions, which do not adequately mimic the in vivo environment. In this study, we used a synthetic polyether-polyurethane matrix to induce the proliferation of pancreatic parenchyma in vivo in diabetic C57BL/6 mice. After chemically inducing diabetes with streptozotocin (STZ), the animals were divided into two groups, with only one group (G2) receiving daily subcutaneous insulin treatment to assess the influence of glycemia on pancreatic proliferation. Both groups (G1 and G2) received synthetic matrices surgically placed adjacent to the native pancreas, which were removed 30 days after implantation. Analyses showed that both groups had islet cells positive for insulin and glucagon, as well as ductal and acinar cells positive for KI-67 and PDX1 in the intra-implant pancreatic tissue. The insulin-treated group exhibited an increase in all these markers, except for the number of KI-67-positive acinar cells. Additionally, a decrease in the expression of adhesion molecules (N-CAD and E-CAD) was observed in this group. The study demonstrated that insulin administration may play a significant role in the proliferation, migration, and transdifferentiation of pancreatic cells within the synthetic polyether-polyurethane matrix model.