Pancreatic Stem Cells and Regenerative Medicine of Endocrine Pancreas

During embryogenesis, the first pancreatic cells arise from a region located in the posterior foregut. Different signals are important to induce the formation of both the ventral and dorsal buds of the pancreas, along with the differentiation of all kinds of pancreatic cells. Other factors are also important to maintain a proliferative pool of pancreatic progenitor cells within the embryonic ductal epithelium. After organogenesis, new beta cells can also be originated by expansion or neogenesis. Different stem cell populations have been described in the pancreas: ductal and acinar cells, nestin-positive cells, hepatocyte growth factor receptor-positive cells, c-Kit-positive cells, and DCAMKL-1-positive cells. Transdifferentiation or dedifferentiation followed by differentiation is also described as being present in the pancreas. Thus, other pancreatic cells that do not belong to the endocrine lineage are possible sources of new beta cells. Extra-pancreatic tissue may also be modified to express insulin, including the hepatic tissue, bone marrow, and monocytes. In addition, stem cells from several sources have been subjected to differentiation protocols, expecting to achieve insulin-producing cells with and without genetic manipulation.