Acquired cell-to-cell coupling and "cardiac-like" calcium oscillations in adult stem cells in a cardiomyocyte microenvironment.
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.
Muller-Borer
Barbara J
BJ
Dept. of Internal Medicine, East Carolina University, Greenville, NC 27834, USA. mullerborerb@ecu.edu
Cascio
Wayne E
WE
Esch
Gwyn L
GL
Grisham
Joe W
JW
Anderson
Page A W
PA
Malouf
Nadia N
NN
D053687:Adult Stem Cells / Q000166:cytology* / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D020013:Calcium Signaling / Q000502:physiology*; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation; D002478:Cells, Cultured; D006329:Heart Conduction System / Q000166:cytology* / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells