Comparison of cell therapy and cytokine therapy for functional repair in ischemic and nonischemic heart failure.
Although cell therapy shows great promise as a new therapeutic strategy for heart failure, its precise mechanisms remain unclear. Furthermore, the advantages of cell therapy over conventional cytokine therapy have yet to be clarified. This study was designed to compare the functional improvement achieved by cell therapy and cytokine therapy in both ischemic and nonischemic heart failure experimental models. Ischemic heart failure was induced by ligating the left anterior descending artery, and nonischemic heart failure was induced by an IP injection of doxorubicin, respectively, in mice. After establishing the heart failure models, mice were randomly given a single intramyocardial injection of 2 x 10(5) c-kit-positive bone marrow stem cells (cell therapy), hepatic growth factor (cytokine therapy), or PBS injection only (control). In the ischemic heart failure model, both cell therapy and cytokine therapy increased the vessel density significantly, inhibited apoptosis of myocytes, and decreased the fibrotic area in the ischemic myocardium, which resulted in a significant increase in the survival rate and enhancement of the cardiac function of these mice (p < 0.05 vs. control therapy). In the nonischemic heart failure model, significant increases in the survival rate and cardiac function were achieved by cell therapy (p < 0.05 vs. control therapy), but not by cytokine therapy, although cytokine therapy inhibited the fibrosis and apoptosis of the cardiomyocytes. Both cell therapy and cytokine therapy are alternative treatments for ischemic heart failure. However, cell therapy is more effective for the treatment of nonischemic heart failure than cytokine therapy achieved by the administration of a single growth factor.
Department of Medical Bioregulation, Division of Cardiovascular Surgery and Medicine, Yamaguchi University School of Medicine, Ube, Yamaguchi 755-8505, Japan. litaoshe@yamaguchi-u.ac.jp
Tao-Sheng
TS
Li
Akihito
A
Mikamo
Masaya
M
Takahashi
Ryo
R
Suzuki
Kazuhiro
K
Ueda
Yasuhiro
Y
Ikeda
Masunori
M
Matsuzaki
Kimikazu
K
Hamano
D000818:Animals; D017209:Apoptosis; D016026:Bone Marrow Transplantation; D016207:Cytokines; D004195:Disease Models, Animal; D006333:Heart Failure / Q000188:drug therapy / Q000209:etiology / Q000628:therapy*; D017228:Hepatocyte Growth Factor / Q000627:therapeutic use*; D051379:Mice; D017202:Myocardial Ischemia / Q000150:complications / Q000188:drug therapy / Q000628:therapy*; D009206:Myocardium / Q000473:pathology; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism
D016207:Cytokines; D017228:Hepatocyte Growth Factor; D019009:Proto-Oncogene Proteins c-kit