Research Project
Grant-in-Aid for Scientific Research (C)
When green fluorescent proteins(GFP) positive skeletal muscle cells were co-cultured with cardiomyocytes some of GFP positive cells expressed cardiac specific troponinT (cTnT), suggesting that skeletal muscle derived cells transdifferentiate into cardiomyocytes. In the first year we examined whether mechanical stress, Ca2+, growth factors, calmodulin and calcineurin effect on the process of transdifferentiation. When the co-cultured cells were treated with niffedipine, calmodulin inhibitors or calcineurin inhibitors the number of cTnT positive skeletal muscle cells decreased. Mechanical stress attenuated the inhibitory effect of niffedipine. In the second year we examined the mechanisms through which skeletal muscle cells acquire the phenotypes of cardiomyocytes by using the co-culture method. When skeletal muscle cells derived from GFP transgenic mouse were co-cultured with cardiomyocytes expressing LacZ gene 70-80% of GFP and cTnT double positive cells expressed b-galacfocidase, sugg … More esting that cell fusion took place. We next examined whether other somatic cells fuse with cardiomyocytes and maintain cardiac phenotypes. When cardiomyocytes were co-cultured with human umbilical vascular endothelial cells(HUVEC) or cardiac fibroblasts some of the cells acquired cardiac phenotypes through cell fusion. During co-culture the ratio of cTnT positive fused cells to the total fused cells increased in time dependent manner. However, the phenotypes of endothelial cells or fibtroblasts in the fused cells were suppressed. When skeletal muscle cells or HUVEC were transplanted into the heart of immunosuppressed rats the fused cells existed in the heart and they expressed cTnT Next we examined whether skeletal muscle-derived stem cells such as side population(SP) cells or Sca-1 positive cells can differentiate into cardiomyocytes. When muscle-derived SP or Sca-1 positive cells were co-cultured with cardiomyocytes the cells acquire the cardiac phenotypes through both fusion and transdifierentiation. However, mono-cultured SP cells or Sca-1 positive cells with various growth factors did not differentiate into cardiomyocytes. Less
All 2005 2004 2003 Other
All Journal Article (19 results) Book (2 results) Publications (6 results)
Nat Med
Pages: 305-311
J Cell Biol 167
Pages: 351-351
J Biol Chem 279
Pages: 11384-11391
J Cell Biol 164
Pages: 395-405
Nature Medicine 11
Arterioscler Thromb Vase Biol 24
Pages: 664-670
Pages: 41095-41103
Arterioscler Thromb Vasc Biol 24
Biochem Biophys Res Commun 305
Pages: 806-810
FASEB J 17
Pages: 1361-1363
Prog Biophys Mol Biol 82
Pages: 57-66
Drugs of Today 39
Pages: 347-357
J Mol Cell Cardiol 35
Pages: 923-960
Circulation 108
Pages: 3024-3030
