The Pancreatic Tissue Regeneration and Molecular Regulators

Hong, Seok Woo; Lee, Song; Park, In Sun

Abstract

Pancreas is a unique organ that produces and secretes digestive enzymes to alimentary tube and supplies endocrine hormones regulating metabolic homeostasis. In the postnatal stage, pancreatic tissue is maintained by a simple proliferation of the preexisting cells. It has been known that tissue regeneration rarely occurs in the normal adult pancreas, particularly in the human pancreas. However regeneration of pancreatic tissue can be induced experimentally following pancreatic injuries in animal models. Regeneration occurs at the site of tissue injury by forming new lobules, so called 'neogenic lobule', that consist of the immature pancreatic tissues of both exocrine and endocrine components. We postulate that regeneration is instigated from the small tubular structures with elongated epithelial cells (neogenic ductules) which grow to ducts and acini for exocrine neogenesis, as well as to islet cells for endocrine tissue formation. As a sequential process of neogenic regeneration, the regenerating tissue becomes heterogeneous in tissue composition. Neogenic lobules in earlier regenerating stage were mainly composed of neogenic ductules which are substituted with developing acini in later stages. The endocrine cells, including insulin secreting beta cells, are also derived from the stem/precursor cells in neogenic ductules. After budding off from the neogenic ductules, the primitive endocrine cells continue to proliferate and differentiate, forming a large cell cluster or primitive islet. Such neogenic regeneration differs, but not completely, from pancreas development during fetal organogenesis. We found that the pancreatic regeneration is regulated by the several biological factors including nestin, clusterin and INGAP which are not involved in embryonic pancreas development. We suggest that the stem/precursor cells are recapitulated and regenerated to functional cells, and stem cell-derived pancreatic regeneration could provide a source of the pancreatic cells, particularly insulin secreting beta cells for cell replacement therapy of diabetes.