Development of human fetal pancreas after transplantation into SCID mice

Only a small component of human fetal pancreas consists of beta cells, and yet this tissue is capable of normalizing the blood glucose levels of diabe tic recipients when transplanted. The time taken to achieve this goal is se veral months, during which time the tissue proliferates and eventually diff erentiates into beta cells. The dynamics of beta cell development have not been described previously. We transplanted human fetal pancreas beneath the renal capsule of immunodeficient mice and analysed the grafts for a period of 12 weeks using antibodies against exocrine cells (lipase), endocrine ce lls and protodifferentiated duct cells. Exocrine cells constituted 48% of a ll epithelial cells in the untransplanted pancreas, with duct cells compris ing 29% and endocrine cells 16% (beta cells 7%). The percentage of exocrine cells declined with time after transplantation, with only a small number u ndergoing apoptosis, and the duct cells increased, the values for these two cell types at 12 weeks being 20 and 57%, respectively. Both cell types app eared to proliferate equally for up to 8 weeks after transplantation, but o nly duct cells thereafter. Endocrine cells began to increase from 8 weeks a fter transplantation, representing 28% of epithelial cells (beta cells 11%) at this time. Intermediate cells, that is, cells expressing the characteri stics of more than one type of mature pancreatic cell, were observed both i n the ungrafted pancreas and after transplantation. The commonest intermedi ate cell type was duct/exocrine, with exocrine/endocrine and duct/endocrine cells also observed, suggesting active transdifferentiation from one cell type to another. We hypothesize that following the transplantation of human fetal pancreatic tissue, exocrine cells mostly transdifferentiate into duc t cells and these eventually develop into endocrine cells, in particular be ta cells. Copyright (C) 2001S.KargerAG,Basel.