ABSTRACT
Pancreatic tissue is maintained by a simple proliferation of the preexisting cells in adulthood, whereas, they are dynamically derived from precursor/ stem cells from ductal epithelia during prenatal life. It has been known that tissue regeneration rarely occurs in the normal adult pancreas, particularly in the human pancreas. However, regeneration can be experimentally induced in the adult pancreas in response to various tissue injuries such as partial resection, pancreatitis by obstruction of the duct, and chemical insults. Regenerating pancreatic tissue shares a common morphogenic feature of "neogenic regeneration" in all regenerating animal models. Neogenic regeneration occurs at the site of tissue injury by forming small tubular structures with elongated epithelial cells (ductules) which grow to form pancreatic ducts and acini. The endocrine cells, including insulin secreting beta cells, are also derived from these ductules. As a sequential process of neogenesis, the regenerating tissue becomes heterogeneous in composition. Some areas were composed by tubules and ductules in surrounding loose connective tissue while others were denser with differentiating acini derived from tubules or ductules. Such neogenic regeneration mimics tissue development during fetal pancreatic organogenesis. In the process of pancreatic neogenesis, we found unique expressions of bioactive proteins such as nestin and clusterin as morphogenic factors. It is likely that the stem/precursor cells could be recapitulated and regenerated to functional cells, including endocrine and exocrine pancreatic cells with acinar and ductal cells during neogenic regeneration of the pancreas.