title: Adult-derived liver stem cells acquire a cardiomyocyte structural and functional phenotype ex vivo.
abstract: We examined the differentiation potential of an adult liver stem cell line (WB F344) in a cardiac microenvironment, ex vivo. WB F344 cells were established from a single cloned nonparenchymal epithelial cell isolated from a normal male adult rat liver. Genetically modified, WB F344 cells that express beta-galactosidase and green fluorescent protein or only beta-galactosidase were co-cultured with dissociated rat or mouse neonatal cardiac cells. After 4 to 14 days, WB F344-derived cardiomyocytes expressed cardiac-specific proteins and exhibited myofibrils, sarcomeres, and a nascent sarcoplasmic reticulum. Further, rhythmically beating WB F344-derived cardiomyocytes displayed calcium transients. Fluorescent recovery after photobleaching demonstrated that WB F344-derived cardiomyocytes were coupled with adjacent neonatal cardiomyocytes and other WB F344-derived cardiomyocytes. Fluorescence in situ hybridization experiments suggested that fusion between WB F344 cells and neonatal mouse cardiomyocytes did not take place. Collectively, these results support the conclusion that these adult-derived liver stem cells respond to signals generated in a cardiac microenvironment ex vivo acquiring a cardiomyocyte phenotype and function. The identification ex vivo of microenvironmental signals that appear to cross germ layer and species specificities should prove valuable in understanding the molecular basis of adult stem cell differentiation and phenotypic plasticity.
authors.affiliation: Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Muller-Borer
authors.forename: Wayne E
authors.initials: WE
authors.lastname: Cascio
authors.forename: Page A W
authors.initials: PA
authors.lastname: Anderson
authors.forename: John N
authors.initials: JN
authors.lastname: Snowwaert
authors.forename: James R
authors.initials: JR
authors.lastname: Frye
authors.forename: Niyati
authors.initials: N
authors.lastname: Desai
authors.forename: Gwyn L
authors.initials: GL
authors.lastname: Esch
authors.forename: Joe A
authors.initials: JA
authors.lastname: Brackham
authors.forename: C Robert
authors.initials: CR
authors.lastname: Bagnell
authors.forename: William B
authors.initials: WB
authors.lastname: Coleman
authors.forename: Joe W
authors.initials: JW
authors.lastname: Grisham
authors.forename: Nadia N
authors.initials: NN
authors.lastname: Malouf
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D002450:Cell Communication; D002454:Cell Differentiation; D002460:Cell Line; D002999:Clone Cells; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000166:cytology; D036681:Fluorescence Recovery After Photobleaching; D005456:Fluorescent Dyes; D049452:Green Fluorescent Proteins; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008099:Liver / Q000166:cytology*; D008164:Luminescent Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism* / Q000648:ultrastructure; D009218:Myosins / Q000378:metabolism; D010641:Phenotype; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D012190:Retroviridae / Q000235:genetics; D012235:Rhodamines; D013234:Stem Cells / Q000166:cytology*; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D005456:Fluorescent Dyes; D008164:Luminescent Proteins; D012235:Rhodamines; D049452:Green Fluorescent Proteins; D001616:beta-Galactosidase; D009218:Myosins; D002118:Calcium