(Journal Article): Adult human cytokeratin 19-positive cells reexpress insulin promoter factor 1 in vitro.
 
Gmyr V, Kerr-Conte J, Belaich S, Vandewalle B, Leteurtre E, Vantyghem MC, Lecomte-Houcke M, Proye C, Lefebvre J, Pattou F (Scientific Research and Teaching Unit 1048, University of Lille 2, France.)
 
IN: Diabetes 2000; 49(10):1671-1680
Impact Factor(s) of Diabetes: 8.848 (2004), 8.298 (2003), 8.256 (2002), 7.7 (2001)

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ABSTRACT: Human pancreatic cells with a typical ductal phenotype and potential to proliferate can be obtained in vitro, but the differentiation capacity of these putative human pancreatic stem cells remains to be documented. We investigated the protein and mRNA expression of insulin promoter factor 1 (IPF-1) (or pancreas/duodenal homeobox 1), a transcription factor critical for pancreatic development and endocrine cell neogenesis, in human pancreatic ductal cells derived from cultured exocrine tissue. In vitro, exocrine cells rapidly adhered (within 12 h) and were de-/transdifferentiated to ductal cells after 3 days with a dramatic loss of amylase protein (n = 4, 92 +/- 3.3%, P < 0.05 vs. day 1) and a simultaneous increase of ductal cytokeratin 19 protein (n = 4, 3.4-fold on day 3 and 7-fold on day 9, P < 0.05 vs. day 1). IPF-1 protein and mRNA levels were low to undetectable in exocrine preparations before culture. After 2 days of culture, a 3.2-fold increase in IPF-1 protein was observed, corresponding to the characteristic 46-kDa protein in Western blots. Reverse transcriptase-polymerase chain reaction confirmed a 10.5-fold increase in IPF-1 mRNA levels after 3 days of culture (n = 5, P < 0.001 vs. day 1). Double immunocytochemistry showed direct evidence that IPF-1 appeared during culture in these exocrine-derived ductal cells (cytokeratin 7-positive) and was not merely in contaminating endocrine cells (chromogranin A-positive). In conclusion, we describe herein the first converging evidence on both the molecular and protein level that human cells with a typical ductal phenotype derived ex vivo from pancreatic exocrine tissue (obtained from healthy donors) can reexpress IPF-1 in culture, suggesting their pancreatic precursor/stem cell potential.

TYPE OF PUBLICATION: Original article

Articles citing this article:

• Street CN, Lakey JR, Rajotte RV, Shapiro AM, Kieffer TJ, Lyon JG, Kin T, Korbutt GS. Enriched Human Pancreatic Ductal Cultures Obtained from Selective Death of Acinar Cells Express Pancreatic and Duodenal Homeobox Gene-1 Age-Dependently. Rev Diabetic Stud 2004. 1: 66-79.
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