Autologous bone marrow cell transplantation improves left ventricular function in rabbit hearts with cardiomyopathy via myocardial regeneration-unrelated mechanisms.
Recent studies suggest transplanted bone marrow cells (BMCs) can be used to reconstitute coronary vessels and myocardium following acute myocardial infarction, thereby improving cardiac function. We sought to investigate the therapeutic potential of BMC transplantation in the treatment of nonischemic cardiomyopathy. Experimental cardiomyopathy was produced by treating rabbits for 8 weeks with doxorubicin (2 mg/kg per week). Two weeks after the treatment was finished, freshly aspirated BMCs or an equivalent volume of phosphate-buffered saline was injected directly into the left ventricular free wall. Four weeks later, heart function was examined during perfusion on a Langendorff apparatus. Left ventricular developed pressure and +/-dp/dt were significantly better in the transplantation group, among which echocardiography also showed significantly better ejection fractions. In addition, left ventricular weights as a fraction of body weight and left ventricular wall thicknesses were both lower in rabbits transplanted with BMCs than in controls. Immunohistochemical analyses carried out 2 weeks after transplantation showed no new myocardium and a very small number of endothelial cells originating from BMCs. On the other hand, immunoblotting revealed upregulated expression of transforming growth factor-beta1 and downregulated expression of matrix metalloproteinase-1 and tumor necrosis factor-alpha following BMC transplantation. In conclusion, autologous BMC transplantation into cardiomyopathic rabbit hearts ameliorates the decline in ventricular function without regenerating cardiomyocytes, most likely by altering expression of various cytokines.
Lu
Chuanjiang
C
Second Department of Medicine, Gifu University, 1-1 Yanagido, Gifu, 501-1194, Japan.
Arai
Masazumi
M
Misao
Yu
Y
Chen
Xuehai
X
Wang
Ningyuan
N
Onogi
Hirohito
H
Kobayashi
Hiroyuki
H
Uno
Yoshihiro
Y
Takemura
Genzou
G
Minatoguchi
Shinya
S
Fujiwara
Takako
T
Fujiwara
Hisayoshi
H
D000818:Animals; D001808:Blood Vessels / Q000502:physiology; D016026:Bone Marrow Transplantation; D009202:Cardiomyopathies / Q000139:chemically induced / Q000503:physiopathology* / Q000601:surgery*; D004317:Doxorubicin; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D011817:Rabbits; D020127:Recovery of Function; D012038:Regeneration; D013318:Stroke Volume; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D016277:Ventricular Function, Left
D014409:Tumor Necrosis Factor-alpha; D004317:Doxorubicin