Bone marrow mononuclear cell transplantation had beneficial effects on doxorubicin-induced cardiomyopathy

Abstract

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.

Conclusion: Bone marrow mononuclear cell transplantation had beneficial effects in doxorubicin-induced cardiomyopathy.