Islet-Derived Fibroblast-Like Cells Are Not Derived via Epithelial-Mesenchymal Transition From Pdx-1 or Insulin-Positive Cells

Islet-Derived Fibroblast-Like Cells Are Not Derived via Epithelial-Mesenchymal Transition From Pdx-1 or Insulin-Positive Cells Lucas G. Chase , Fernando Ulloa-Montoya , Benjamin L. Kidder and Catherine M. Verfaillie From the Stem Cell Institute, University of Minnesota, Minneapolis, Minnesota Address correspondence and reprint requests to Catherine M. Verfaillie Stem Cell Institute, University of Minnesota, McGuire Translational Research Facility, 2001 6th St. SE, mail code 2873, Minneapolis, MN 55455. E-mail: verfa001{at}umn.edu Abstract As recent studies suggest that newly formed pancreatic β-cells are a result of self-duplication rather than stem cell differentiation, in vitro expansion of β-cells presents a potential mechanism by which to increase available donor tissue for cell-based diabetes therapies. Although most studies have found that β-cells are resilient to substantial in vitro expansion, recent studies have suggested that it is possible to expand these cells through a process referred to as epithelial-mesenchymal transition (EMT). To further substantiate such an expansion mechanism, we used recombination-based genetic lineage tracing to determine the origin of proliferating fibroblast-like cells from cultured pancreatic islets in vitro. We demonstrate, using two culture methods, that EMT does not underlie the appearance of fibroblast-like cells in mouse islet cultures but that fibroblast-like cells appear to represent mesenchymal stem cell (MSC)-like cells akin to MSCs isolated from bone marrow. BM-MSC, bone marrow mesenchymal stem cell CAAGS, chicken β-actin promoter/cytomegalovirus enhancer EMT, epithelial-mesenchymal transition FACS, fluorescence-activated cell sorter GFP, green fluorescent protein MSC, mesenchymal stem cell qPCR, quantitative PCR Footnotes Additional information for this article can be found in an online appendix at http://diabetes.diabetesjournals.org . Posted on the World Wide Web at http://diabetes.diabetesjournals.org on 16 November 2006. See accompanying commentary on p. 281. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Accepted October 6, 2006. Received August 17, 2006. DIABETES