Our team wants to find ways to generate new insulin-producing, glucose-regulated "beta" cells that can be used for transplantation in diabetes patients and ways to regenerate beta cells in the pancreas. We study rodent experimental models as well as human cells. The first aim is based on tissue engineering starting from: 1. Exocrine pancreatic cells: reprogramming of adult exocrine cells to endocrine cells, or transdifferentiation in culture. 2. Embryonic stem cells: directed differentiation by mimicking the embryonic environment in culture. Cell differentiation is driven in these models by addition of extracellular agents like growth factors, cytokines, hormones and extracellular matrix components. These studies include the phenotypic and functional characterization of the obtained (human) beta cells and their transplantation in animal models. The second aim is based on experimental animal models: 1. Pancreatic duct ligation, a "neogenesis" model that has been developed in our group and mimicks pancreatitis; it is the model that induces the most robust expansion of the beta cell mass. 2. Diabetic mice. In both models, we want to discover the progenitor cells from which new beta cells can be regenerated, and the extracellular factors that regulate the associated events (cell proliferation, differentiation, migration).