Modulation of rat pancreatic acinoductal transdifferentiation and expression of PDX-1 in vitro

Aims/hypothesis. In adult pancreatic regeneration models exocrine acini are found to transdifferentiate to duct-like complexes. This has also been ass ociated with the formation of new endocrine islet cells. We aimed to establ ish an in vitro model in which this transdifferentiation process is charact erised and can be modulated. Methods. Purified rat pancreatic acini were cultured in suspension. Differe ntiation was analysed by immunocytochemistry, electron microscopy, western blotting and RT-PCR. Results. During culture acinar cells directly transdifferentiated without d ividing, the cells lost their acinar phenotype and started to express cytok eratins 20 and 7 and fetal liver kinase-l (Flk-1) receptors for vascular en dothelial growth factor. Expression of the acinar pancreatic exocrine trans cription factor (PTF-1) remained and the pancreatic duodenal homeobox-conta ining transcription factor (PDX-1) was induced. When transdifferentiation w as completed, the cells started to express protein gene product 9.5, a pann euroendocrine marker. By combining these features, the transdifferentiated cells show similar characteristics to precursor cells during active beta-ce ll neogenesis. We were able to modulate the differentiation state by additi on of nicotinamide or sodium butyrate, agents which are known to stimulate endocrine differentiation in other models. Conclusion/interpretation. Here, we present an in vitro system in which the cellular differentiation of putative pancreatic endocrine precursor cells and their PDX-1 expression can be modulated, thereby providing a possible m odel for the study of beta-cell transdifferentiation.