The transplanted fetal endocrine pancreas undergoes an inherent sequentialdifferentiation similar to that in the native pancreas - An ultrastructural study in the pig-to-mouse model

This study examines, at the ultrastructural level, whether the fetal porcin e endocrine pancreas (insulin, glucagon, somatostatin, and pancreatic polyp eptide [PP]- and islet amyloid polypeptide [IAPP]-containing cells) develop s normally after transplantation under the kidney capsule in athymic mice. We have thus used an in vivo pig-to-mouse model for the differentiation of the endocrine pancreas removed from its normal milieu. Islet-like cell clus ters (ICCs) mere prepared from the fetal porcine pancreas as previously des cribed and transplanted under the renal capsule of athymic mice. At various times after transplantation, the endocrine pancreas was removed and the le vel of differentiation was compared with the native pancreas of the same bi ological age. At the ultrastructural level, several sequential steps could be identified based on the morphology and hormone content of the secretory granules of the endocrine cell examined. Applying this approach, we could d emonstrate that the ontogeny of the transplanted fetal pig pancreas follows the same sequential differentiation as the native pancreas. The process se ems to be under stringent control, apparently directly related to the biolo gical age of the tissue, and independent not only of the new environment un der the kidney capsule but also of the adult and xenogeneic milieu provided after transplantation to the athymic nude mouse. Therefore, all four major hormone-producing cells seem to develop normally after transplantation whe n compared with the development in the native pancreas. IAPP was produced b y the pluripotent fetal endocrine cells as well as the adult alpha-, beta-, and delta -cell granules in the native pancreas; however, in the transplan ted pancreas, IAPP expression was demonstrated only in beta -cells, delta - cells, and PP cells. No IAPP was found in granules of the alpha -cell Linea ge. The results suggest a sequential differentiation of all four major type s of islet cells from a common pluripotent progenitor cell, which seems to be located in the pancreatic ducts. Therefore, the results presented strong ly suggest that the ontogeny of the four major endocrine islet cells is det ermined by genetic information carried by the progenitor cells and not by t he systemic or local environment.