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(American Journal of Pathology. 2004;165:135-145.)
© 2004 American Society for Investigative Pathology

Adult-Derived Liver Stem Cells Acquire a Cardiomyocyte Structural and Functional Phenotype ex Vivo

Barbara J. Muller-Borer*, Wayne E. Cascio*, Page A.W. Anderson{dagger}, John N. Snowwaert{ddagger}, James R. Frye§, Niyati Desai§, Gwyn L. Esch§, Joe A. Brackham§, C. Robert Bagnell§, William B. Coleman§, Joe W. Grisham§ and Nadia N. Malouf§

From the Departments of Medicine,* Genetics,{ddagger} and Pathology and Laboratory Medicine,§ University of North Carolina at Chapel Hill, Chapel Hill; and the Department of Pediatrics,{dagger} Duke University Medical Center, Durham, North Carolina

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 ß-galactosidase and green fluorescent protein or only ß-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.




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B. J. Muller-Borer, W. E. Cascio, G. L. Esch, H.-S. Kim, W. B. Coleman, J. W. Grisham, P. A. W. Anderson, and N. N. Malouf
Mechanisms controlling the acquisition of a cardiac phenotype by liver stem cells
PNAS, March 6, 2007; 104(10): 3877 - 3882.
[Abstract] [Full Text] [PDF]


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