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Pancreas  - Development and Stem Cells


Embryonic Development of the Pancreas:

A thickening of the endoderm opposite the hepatic bulge on the dorsal foregut endoderm is the earliest morphological sign of the developing pancreas, and takes place at E8.75-E9.0. This process marks the formation of the dorsal pancreatic bud. The thickening then begins to bulge into the surrounding mesenchyme at E9.5, followed by the development of paired ventral pancreatic buds, which derive from the ventral foregut endoderm at E10 (in mammals the left bud usually regresses but contributes to the mature organ in chick pancreatic development). The primary transition stage of pancreatic development (first wave) occurs between E9.5-E12.5 in the mouse and is characterized by proliferation of pancreatic progenitor cells that gives rise to a stratified epithelium plexus, with projections into the mesenchyme. During this time, gut tube twisting brings the dorsal and ventral buds together, setting the ground for their future merger into one organ. The secondary transition (second wave) begins at E13.5, whereby epithelial cells undergo a differentiation process and commit to the major pancreatic lineages. Acinar cells arise from the extending tip epithelium and huge numbers of acini are produced and continue proliferating past E16.5.

Mature islets of Langerhans are formed in the late stages of gestation and are continually formed during the first postnatal weeks. While the anatomy of rodent pancreatic islets typically consists of a beta cell core surrounded by α, δ and PP cells, with interspersed ε-cells, segregation of cell types in the human pancreatic islet is less defined. Recently, a sixth endocrine cell type has been identified as a gastrin producing G-cell.

Additional tissues and cells that contribute to the pancreas include smooth muscles, fibroblasts and lymphatics, which presumably originate in the surrounding mesenchyme.

Anatomical Structure and Function of the Pancreas:

The pancreas is an organ with complex roles in regulation of both nutrient metabolism and glucose homeostasis. It is also implicated in two major diseases - diabetes mellitus and pancreatic cancer.

The pancreas is of endodermal origin and is generally divided into into two distinct types of glandular tissue with distinct function- paracrine (secrete enzymes into the intestine) and exocrine (secrete hormones into the bloodstream). The exocrine, enzyme-secreting cells are arranged as clusters called acini. The acinar secretory granules contain over 20 types of digestive enzymes, most in the form of inactive precursors, which are secreted and collected by the branching ductal system. Mitochondria-rich, low cuboidal centroacinar cells secrete additional components of the pancreatic juice into the intestinal system, via a branching duct system. 

The endocrine cells form islets of Langerhans within the exocrine tissue and include six cell types: α cells, which secrete glucagon, β cells, which secrete insulin and its antagonist amylin, δ cells, which secrete somatostatin, ε cells, which secrete ghrelin, pancreatic polypeptide (f) cells (which are mainly derived from the ventral pancreatic bud of the embryo- unlike the other endocrine cell types which are derived from both the ventral and dorsal pancreatic buds) and secrete the pancreatic polypeptide, and finally the newly discovered gastrin-producing G cells.

Interestingly, in vertebrates, insulin-producing cells develop from endoderm, whereas in flies they develop from ectoderm.