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Updated: Aug 25, 2026
A Doxorubicin-Induced Murine Model of Dilated Cardiomyopathy In Vivo
Published on: May 16, 2020
Bone marrow mononuclear cell transplantation had beneficial effects on doxorubicin-induced cardiomyopathy
Michiko Ishida1, Shinji Tomita, Takeshi Nakatani
1Department of Regenerative Medicine and Tissue Engineering, National Cardiovascular Center, Osaka, Japan.
Insights
Bone marrow mononuclear cell (BMMNC) transplantation improved cardiac function and attenuated heart failure in a rat model of doxorubicin-induced cardiomyopathy. This study highlights BMMNCs as a potential therapy for non-ischemic heart failure.
Area of Science:
- Cardiology
- Regenerative Medicine
- Cell Therapy
Background:
- Cell transplantation shows promise for end-stage heart failure.
- Bone marrow mononuclear cells (BMMNCs) are known to promote angiogenesis in ischemic heart disease.
- The efficacy of BMMNC transplantation in non-ischemic dilated cardiomyopathy remains unexplored.
Purpose of the Study:
- To evaluate the therapeutic potential of BMMNC transplantation in a rat model of doxorubicin-induced cardiomyopathy.
- To assess the impact of BMMNCs on cardiac function and structure in a non-ischemic heart failure model.
Main Methods:
- Doxorubicin was administered to induce cardiomyopathy in Lewis rats.
- Rats were divided into transplant (BMMNC), control (saline), and sham groups.
- Echocardiography, Langendorff apparatus, radioimmunoassay, and histology (including electron microscopy) were used for assessment.
Main Results:
- BMMNC transplantation (TX group) increased left ventricular wall thickness and improved systolic and developed pressures.
- While direct comparison with the control group showed no significant difference in some parameters, the TX group exhibited the most attenuated secondary effects of heart failure.
- Histological analysis revealed increased vascular density and better myocardial preservation in the TX group.
Conclusions:
- Bone marrow mononuclear cell transplantation demonstrated beneficial effects in doxorubicin-induced cardiomyopathy.
- BMMNC transplantation may be a viable therapeutic strategy for non-ischemic heart failure.
- Further research is warranted to explore the mechanisms and clinical applicability of BMMNC therapy.
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.
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