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Acquired Cell-to-Cell Coupling and "Cardiac-Like" Calcium Oscillations in Adult Stem Cells in a Cardiomyocyte Microenvironment

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6 Author(s)
Muller-Borer, B.J. ; Dept. of Internal Medicine, East Carolina Univ., Greenville, NC ; Cascio, W.E. ; Esch, G.L. ; Grisham, J.W.
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Adult-derived stem cells have recently been found to respond in vivo to inductive signals from the microenvironment and to differentiate into a phenotype that is characteristic of cells in that microenvironment. We examined the differentiation potential of an adult liver stem cell line (WBF344) in a cardiac microenvironment in vitro. WBF344 cells were established from a single cloned non-parenchymal epithelial cell isolated from a normal male adult rat liver. Genetically modified, WBF344 cells that express beta-galactosidase, green fluorescent protein (GFP) or mitochondrial red fluorescent protein (DsRed) were co-cultured with rat neonatal cardiac cells. After 4-14 days, we identified WBF344-derived cardiomyocytes that were elongated, binucleated and expressed the cardiac specific proteins cardiac troponin T, cardiac troponin I and N cadherin. These WBF344-derived cardiomyocytes also exhibited myofibrils, sarcomeres, and a nascent sarcoplasmic reticulum. Furthermore, rhythmically beating WBF344-derived cardiomyocytes displayed "cardiac-like" calcium transients similar to the surrounding neonatal cardiomyocytes. Fluorescent recovery after photobleaching demonstrated that WBF344-derived cardiomyocytes were electrically coupled with adjacent neonatal cardiomyocytes through gap junctions (GJs). Collectively, these results support the conclusion that these adult-derived liver stem cells respond to signals generated in a cardiac microenvironment in vitro acquiring a cardiomyocyte phenotype and function. The identification of micro-environmental signals that appear to cross germ layer and species specificities should prove valuable in understanding the regulation of normal development and stem cell differentiation in vivo

Published in:

Engineering in Medicine and Biology Society, 2006. EMBS '06. 28th Annual International Conference of the IEEE

Date of Conference:

Aug. 30 2006-Sept. 3 2006