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Published online 18 October 2004. doi:10.1083/jcb.200312111
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 167, Number 2, 351-363
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Article

 Cardiomyocytes fuse with surrounding noncardiomyocytes and reenter the cell cycle

Katsuhisa Matsuura1,2, Hiroshi Wada1, Toshio Nagai1, Yoshihiro Iijima1, Tohru Minamino1, Masanori Sano1, Hiroshi Akazawa1, Jeffery D. Molkentin3, Hiroshi Kasanuki2, and Issei Komuro1

1 Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan
2 Department of Cardiology, The Heart Institute of Japan, Tokyo Women's Medical University, Tokyo 162-8666, Japan
3 Division of Molecular Cardiovascular Biology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229

Correspondence to Issei Komuro: komuro-tky{at}umin.ac.jp

The concept of the plasticity or transdifferentiation of adult stem cells has been challenged by the phenomenon of cell fusion. In this work, we examined whether neonatal cardiomyocytes fuse with various somatic cells including endothelial cells, cardiac fibroblasts, bone marrow cells, and endothelial progenitor cells spontaneously in vitro. When cardiomyocytes were cocultured with endothelial cells or cardiac fibroblasts, they fused and showed phenotypes of cardiomyocytes. Furthermore, cardiomyocytes reentered the G2-M phase in the cell cycle after fusing with proliferative noncardiomyocytes. Transplanted endothelial cells or skeletal muscle–derived cells fused with adult cardiomyocytes in vivo. In the cryoinjured heart, there were Ki67-positive cells that expressed both cardiac and endothelial lineage marker proteins. These results suggest that cardiomyocytes fuse with other cells and enter the cell cycle by maintaining their phenotypes.

K. Matsuura and H. Wada contributed equally to this paper.

Abbreviations used in this paper: ANF, atrial natriuretic factor; ß-gal, ß-galactosidase; CAT, chloramphenicol acetyltransferase; cFB, cardiac fibroblasts; cTnT, cardiac troponin T; EPC, endothelial progenitor cell; HUVEC, human umbilical vein endothelial cells; PH3, phosphohistone H3; RFP, red fluorescent protein; UEA-1, ulex europaeus agglutinin-1; vWF, von Willebrand factor.


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