on April 28, 2005
Published online before print April 28, 2005, doi: 10.1161/01.ATV.0000168409.69960.e9
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Submitted on January 24, 2005
Accepted on March 17, 2005
Niche-Dependent Translineage Commitment of Endothelial Progenitor Cells, Not Cell Fusion in General, Into Myocardial Lineage Cells
Satoshi Murasawa ;
From the Department of Regenerative Medicine (S.M., A.K., M.H., S.N., T.A.), Institute of Biomedical Research and Innovation/Stem Cell Translational Research, RIKEN Center for Developmental Biology, Kobe, Japan; and the Department of Physiology (T.A.), Tokai University School of Medicine, Japan.
* To whom correspondence should be addressed. E-mail: asa777{at}aol.com.
Objective--Previous studies from our laboratory have shown therapeutic potential of ex vivo expanded endothelial progenitor cells (EPCs) for myocardial ischemia. Our purpose was to investigate the mechanisms regulating EPC contribution to myocardial regeneration.
Methods and Results--To evaluate niche-dependent expression profiles of EPCs in vitro, we performed coculture using cultured EPCs derived from human peripheral blood and rat cardiac myoblast cell line (H9C2). Reverse-transcription polymerase chain reaction (PCR) disclosed the expression of human-specific cardiac markers as well as human-specific smooth muscle markers. Cytoimmunochemistry presented several cocultured cells stained with human specific cardiac antibody. To prove this translineage differentiation in vivo, human cultured EPCs were injected into nude rat myocardial infarction model. Reverse-transcription PCR as well as immunohistochemistry of rat myocardial samples demonstrated the expression of human specific cardiac, vascular smooth muscle, and endothelial markers. We observed the distribution of colors (Qtracker; Quantum Dot Corp) in coculture to detect the fused cells, and the frequency of cell fusion was <1%.
Conclusions--EPCs can contribute to not only vasculogenesis but also myogenesis in the ischemic myocardium in vivo. Transdifferentiation, not cell fusion, is dominant for EPCs commitment to myocardial lineage cells. Ex vivo expanded EPCs transplantation might have enhanced therapeutic potential for myocardial regeneration.
Key words: cardiovascular diseases • endothelial • myocardium • regeneration • stem cells • vasculogenesis
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