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No Evidence for Mouse Pancreatic ß-Cell Epithelial-Mesenchymal Transition In Vitro

From the Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases/National Institutes of Health, Bethesda, Maryland

Address correspondence and reprint requests to Nadya Lumelsky, Center for Biotechnology and Innovation, National Institute of Dental and Craniofacial Research/National Institutes of Health, 45 Center Dr., Room 4An. 24J, Bethesda, MD 20892. E-mail: nadyal{at}nidcr.nih.gov

Abbreviations: EGFP; enhanced green fluorescent protein; EMT, epithelial-mesenchymal transition; FACS, fluorescence-activated cell sorting; hIPC, human islet progenitor cell; IEF, islet-enriched fraction

We used cre/loxP-based genetic lineage tracing analysis to test a previously proposed hypothesis that in vitro cultured adult pancreatic ß-cells undergo epithelial-mesenchymal transition (EMT) to generate a highly proliferative, differentiation-competent population of mesenchymal islet "progenitor" cells. Our results in the mouse that are likely to be directly relevant to the human system show that adult mouse ß-cells do not undergo EMT in vitro and that the mesenchymal cells that arise in cultures of adult pancreas are not derived from ß-cells. We argue that these cells most likely originate from expansion of mesenchymal cells integral to the heterogeneous pancreatic islet preparations. As such, these mesenchymal "progenitors" might not represent the best possible source for generation of physiologically competent ß-cells for treatment of diabetes.

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