FIBROBLAST GROWTH FACTORS 1 AND 2 ACT ON THE IMMATURE HUMAN FETAL ISLET CELL BUT NOT ON THE MATURE β-CELL

Fibrpblast growth factors (FGFs) play an important role in the embryogenesis of many organs. In order to elucidate the regulation of pancreatic islet development, we have used tissue culture of human fetal pancreas to study the effects of FGFs. Our method is based on the formation of islet-like cell clusters (ICCs), consisting of 87% undifferentiated cells and 13% islet hormone-positive cells. Supplementation of the culture medium with FGF-2 (basic FGF) more than doubled the formation of ICCs, stimulated their DNA synthesis, inhibited the insulin release (ED50-1 ng/ml), but did not affect the insulin content. This activity was shared by FGF-1 (acidic FGF) but not by FGF-6 or FGF-7 (KGF). When ICCs were treated for 72h with bFGF-Saporin (F-SAP), a mitotoxin targeted against FGF-receptor expressing cells, a distinct population (45%) of cells within the ICCs were killed, whereas some strongly hormone-positive (mature) islet cells were left intact. F-SAP treatment also blocked the endocrine differentiation induced by nicotinamide. Similar experiments with isolated adult human islets showed no activity of FGF-2 or F-SAP, supporting a role for FGF in the early development of human islet cells.