Embryogenesis and neogenesis of the endocrine pancreas : the role of c-met, c-kit and nestin positive cells

The present study was undertaken to study the expression of nestin, c-met and c-kit in the embryogenesis and the development and growth of the adult pancreas. The rationality for doing these studies was that these proteins were included in the development of the pancreas and of other organ structure and some of them had even been proposed to be present on precursor cells. Therefore we have performed a few experiments to elucidate the role of these proteins.
We have found that heterogenous populations of c-met and c-kit positive cells may contain some cells that may have curative effects and could differentiate into beta-cells.

In vitro experiments showed that nestin, c-met and c-kit positive cells are expressed on different locations in the pancreas during embryogenesis, neogenesis and adult growth.
Moreover, we found that these cells express specific proteins that are specific for pancreatic (precursor cells) (Islet-1, ngn3, Pax4, Pax6, amylase, Pdx-1, insuline, PP/SOM en glucagon), endothelial cells (CD31) en nerve cells (β3-tubulin).
Ex vivo differentiation experiments showed that differentiated c-met cells appeared to be in a more immature beta-cells stage than differentiated c-kit cells, since the former cells still express Pax6 and Pax4, whereas in differentiated c-kit cells the expression of these transcription factors disappeared. This demonstrates that this heterogeneous population of cells with a specific unique lineage restricted differentiation can be forced to redirect their differentiation and gain a more beta-cell like phenotype.

Thus, nestin, c-met and c-kit positive cells may have therapeutic potentials and may be involved in regeneration processes of the pancreas.

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	Engelse samenvatting
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	Dankwoord
	Curriculum vitae
	Volledige dissertatie

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