Fibroblast growth factors 7 and 10 are expressed in the human embryonic pancreatic mesenchyme and promote the proliferation of embryonic pancreatic epithelial cells.
OBJECTIVE
The fibroblast growth factor (FGF) family consists of 22 members. In rodents, several FGFs are expressed in the pancreas, where they participate in epithelial-mesenchymal interactions. Our objective was to describe the pattern of expression of FGFs in the human embryonic pancreas and to analyse their effect on pancreas development.


METHODS
The expression of FGFs was analysed by RT-PCR. To investigate the cell types expressing FGF7 and FGF10, we separated epithelial from mesenchymal cells using immunomagnetic beads linked to E-cadherin antibodies and performed real-time PCR. The effect of FGF7 and FGF10 on proliferation of human embryonic pancreatic epithelial cells was evaluated in vitro by measuring BrdU incorporation.


RESULTS
We found that different FGFs are expressed in the human embryonic pancreas, and we focused on FGF7 and FGF10. We defined a new approach to separating epithelial cells (containing the pancreatic progenitor cells) from mesenchymal cells. This allowed us to demonstrate that human embryonic pancreatic mesenchymal cells express both FGF7 and FGF10. We next demonstrated that FGF7 and FGF10 were able to induce the proliferation of the epithelial cells in vitro.


CONCLUSIONS
These findings indicate that it is now possible to efficiently separate human embryonic pancreatic epithelial from mesenchymal cells, an important step to characterize and expand progenitor cells. This method allowed us to demonstrate that human embryonic pancreatic mesenchyme expresses FGF7 and FGF10 that act on epithelial cells to activate their proliferation. Such growth factors could thus be used to expand human embryonic pancreatic epithelial cells.
Ye
F
F
Faculty Necker, INSERM E363, 156 Rue de Vaugirard, 75015 Paris, France.
Duvillié
B
B
Scharfmann
R
R
D001483:Base Sequence; D015820:Cadherins / Q000235:genetics; D002455:Cell Division; D021983:Cyclophilins / Q000235:genetics; D017931:DNA Primers; D004847:Epithelial Cells / Q000166:cytology*; D051526:Fibroblast Growth Factor 10; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008648:Mesoderm / Q000502:physiology; D010179:Pancreas / Q000166:cytology* / Q000196:embryology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014746:Vimentin / Q000235:genetics
D015820:Cadherins; D017931:DNA Primers; C496463:FGF10 protein, human; C496453:FGF7 protein, human; D051526:Fibroblast Growth Factor 10; D014746:Vimentin; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D021983:Cyclophilins