Bone marrow mononuclear cell transplantation had beneficial effects on doxorubicin-induced cardiomyopathy.
BACKGROUND
Cell transplantation is a promising therapy for treating end-stage heart failure. Bone marrow mononuclear cells (BMMNC) have been used to enhance angiogenesis in ischemic heart disease. However, the effect of BMMNC transplantation in non-ischemic dilated cardiomyopathy is unknown. In this study, we evaluated the efficacy of BMMNC transplantation in doxorubicin-induced cardiomyopathy in a rat model.


METHODS
Doxorubicin (15 mg/kg, IP) was introduced into 52 Lewis rats. They were divided into 3 groups at 4 weeks after injection: transplant group (TX, BMMNC [1 x 10(6)] implantation, n = 18), control group (CN, saline injection, n = 18), and sham group (SH, thoracotomy, n = 16). At 4 weeks after surgery, we used echocardiography to measure systolic left ventricular diameter (LVDs), diastolic left ventricular diameter (LVDd), fractional shortening (FS), and left ventricular wall thickness/LVDs. We used a Langendorff apparatus to measure systolic, diastolic, and developed pressures. We used radioimmunoassay to measure circulating atrial natriuretic peptide concentration, and we performed histologic study, including electron-microscopic study.


RESULTS
Left ventricular wall thickness/LVDs in the TX group was the largest of all groups (p < 0.05). Systolic and developed pressures in the TX group were the greatest (p < 0.005). Systolic left ventricular diameter, FS, and end-diastolic pressure in the TX group were smaller than in the SH group (p < 0.05). These cardiac parameters did not differ significantly between TX and CN groups, but secondary changes (decreased heart weight, developed ascites, and increased atrial natriuretic peptide concentration) caused by doxorubicin-induced heart failure were most attenuated in the TX group. In the TX group, vascular density was greatest (p < 0.05) in the left ventricular free wall and in the septum. In addition, electron microscopy showed that myocardium in the TX group was most maintained.


CONCLUSIONS
Bone marrow mononuclear cell transplantation had beneficial effects in doxorubicin-induced cardiomyopathy.
Ishida
Michiko
M
Department of Regenerative Medicine and Tissue Engineering, National Cardiovascular Center, Osaka, Japan.
Tomita
Shinji
S
Nakatani
Takeshi
T
Fukuhara
Shinya
S
Hamamoto
Masaki
M
Nagaya
Noritoshi
N
Ohtsu
Yoshinori
Y
Suga
Michiharu
M
Yutani
Chikao
C
Yagihara
Toshikatsu
T
Yamada
Kazuhiko
K
Kitamura
Soichiro
S
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood; D016026:Bone Marrow Transplantation; D002311:Cardiomyopathy, Dilated / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D003326:Coronary Circulation; D004195:Disease Models, Animal; D004317:Doxorubicin; D006334:Heart Function Tests; D006339:Heart Rate; D008297:Male; D009206:Myocardium / Q000473:pathology / Q000648:ultrastructure; D018919:Neovascularization, Physiologic; D051381:Rats; D011917:Rats, Inbred Lew; D017725:Ventricular Pressure
D004317:Doxorubicin; D009320:Atrial Natriuretic Factor