Transplantation of cardiac progenitor cells ameliorates cardiac dysfunction after myocardial infarction in mice
| Autor: | Atsushi Honda, Masakuni Tokunaga, Nobuhisa Hagiwara, Hiroshi Kasanuki, Teruo Okano, Noritoshi Fukushima, Tatsuya Shimizu, Toshio Nagai, Katsuhisa Matsuura, Koji Iwanaga, Issei Komuro |
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| Rok vydání: | 2008 |
| Předmět: |
Cardiac function curve
Male Vascular Endothelial Growth Factor A Integrins Angiogenesis Cell Survival Cellular differentiation Myocardial Infarction Vascular Cell Adhesion Molecule-1 Biology Integrin alpha4beta1 Cell therapy Mice Cell Movement Myocyte Animals Myocytes Cardiac Progenitor cell Cells Cultured Cell Differentiation General Medicine Rats Transplantation Mice Inbred C57BL Immunology Cancer research Female Stem cell Stem Cell Transplantation Research Article |
| Zdroj: | The Journal of clinical investigation. 119(8) |
| ISSN: | 1558-8238 |
| Popis: | Cardiac progenitor cells are a potential source of cell therapy for heart failure. Although recent studies have shown that transplantation of cardiac stem/progenitor cells improves function of infarcted hearts, the precise mechanisms of the improvement in function remain poorly understood. The present study demonstrates that transplantation of sheets of clonally expanded stem cell antigen 1-positive (Sca-1-positive) cells (CPCs) ameliorates cardiac dysfunction after myocardial infarction in mice. CPC efficiently differentiated into cardiomyocytes and secreted various cytokines, including soluble VCAM-1 (sVCAM-1). Secreted sVCAM-1 induced migration of endothelial cells and CPCs and prevented cardiomyocyte death from oxidative stress through activation of Akt, ERK, and p38 MAPK. Treatment with antibodies specific for very late antigen-4 (VLA-4), a receptor of sVCAM-1, abolished the effects of CPC-derived conditioned medium on cardiomyocytes and CPCs in vitro and inhibited angiogenesis, CPC migration, and survival in vivo, which led to attenuation of improved cardiac function following transplantation of CPC sheets. These results suggest that CPC transplantation improves cardiac function after myocardial infarction through cardiomyocyte differentiation and paracrine mechanisms mediated via the sVCAM-1/VLA-4 signaling pathway. |
| Databáze: | OpenAIRE |
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