Islet-derived fibroblast-like cells are not derived via epithelial-mesenchymal transition from Pdx-1 or insulin-positive cells.
As recent studies suggest that newly formed pancreatic beta-cells are a result of self-duplication rather than stem cell differentiation, in vitro expansion of beta-cells presents a potential mechanism by which to increase available donor tissue for cell-based diabetes therapies. Although most studies have found that beta-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.
Chase
Lucas G
LG
Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USA.
Ulloa-Montoya
Fernando
F
Kidder
Benjamin L
BL
Verfaillie
Catherine M
CM
D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002455:Cell Division; D018076:DNA, Complementary / Q000235:genetics; D004847:Epithelial Cells / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology* / Q000502:physiology*; D005434:Flow Cytometry; D018398:Homeodomain Proteins / Q000502:physiology*; D018960:Hyaluronan Receptors / Q000032:analysis; D007328:Insulin / Q000502:physiology*; D007515:Islets of Langerhans / Q000166:cytology* / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000032:analysis; D008648:Mesoderm / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D015534:Trans-Activators / Q000502:physiology*
D018076:DNA, Complementary; D018398:Homeodomain Proteins; D018960:Hyaluronan Receptors; D007328:Insulin; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; D012313:RNA; D017493:Leukocyte Common Antigens