title: Low-Density Lipoprotein Uptake Demonstrates a Hepatocyte Phenotype in the Dog, but Is Nonspecific.
abstract: Low-density lipoprotein (LDL) uptake is one of a number of tests used to demonstrate hepatocyte-like function after stem cell differentiation. Use of two compounds, LDL and acetylated LDL (AcLDL), has been described despite each having different mechanisms of uptake. Three primary hepatocyte cultures and three sets of mesenchymal stromal cell (MSC) cultures, derived from both adipose tissue and bone marrow, were harvested from dogs. Those cells were compared to commercially available human and mouse bone marrow-derived MSCs. LDL receptor expression was demonstrated by gene expression and immunofluorescence in all primary hepatocyte cultures, undifferentiated canine bone marrow MSCs and canine adipose MSCs. Undifferentiated human and mouse bone marrow MSCs also expressed the LDL receptor. In vitro, canine hepatocytes took up labeled LDL, but not AcLDL. All undifferentiated MSCs took up LDL, but not AcLDL. In conclusion, LDL and not AcLDL is a test of canine hepatocyte-like phenotype, but this is not tissue or species specific and, therefore, is not informative assay when testing proof of MSC to hepatocyte differentiation.
authors.affiliation: 1 Royal (Dick) School of Veterinary Studies, The Roslin Institute, The University of Edinburgh , Midlothian, United Kingdom .
authors.forename: Adam G
authors.initials: AG
authors.lastname: Gow
authors.affiliation: 1 Royal (Dick) School of Veterinary Studies, The Roslin Institute, The University of Edinburgh , Midlothian, United Kingdom .
authors.forename: Rhona
authors.initials: R
authors.lastname: Muirhead
authors.affiliation: 2 MRC Center for Regenerative Medicine, The University of Edinburgh , Edinburgh, United Kingdom .
authors.forename: David C
authors.initials: DC
authors.lastname: Hay
authors.affiliation: 1 Royal (Dick) School of Veterinary Studies, The Roslin Institute, The University of Edinburgh , Midlothian, United Kingdom .
authors.forename: David J
authors.initials: DJ
authors.lastname: Argyle
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism / Q000502:physiology; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D004285:Dogs; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D008077:Lipoproteins, LDL / Q000493:pharmacokinetics*; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000502:physiology; D051379:Mice; D009928:Organ Specificity; D010641:Phenotype; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism
chemical_list: D008077:Lipoproteins, LDL; D011973:Receptors, LDL; C032629:acetyl-LDL