Angiogenesis without Functional Outcome after Mononuclear Stem Cell Transplant in a Doxorubicin-Induced Dilated Myocardiopathy Murine Model

Abstract

Objectives

Cell transplantation is considered a novel approach in the treatment of myocardiopathy. The objective of this study was to evaluate the effects of autologous mononuclear stem cell therapy in doxorubicin-induced dilated myocardiopathy by conducting both functional and histopathologic analysis.

Methods

Seventy male rats were doxorubicin injected intraperitoneally for 2 weeks. At 1 month, the animals that had demonstrated left ventricular ejection fractions less than 40% were randomly divided into a mononuclear stem cell group and controls. Mononuclear stem cells were isolated. All animals underwent echocardiographic study: baseline, pre-cell therapy, and at 1 month post-cell therapy, and analyzed by the nonparametric Mann-Whitney test. Transplants were performed by subepicardial injections. Standard staining was performed.

Results

Twenty-three animals were randomly treated: mononuclear stem cell and control groups, with 11 rats completing the study. Cell viability was 85%. Mononuclear stem cells (n=5; 5×10⁶ cells /300 μL medium) and control (n=6; 300 μL medium) were used. The resulting left ventricular ejection fraction in the cell therapy group was not significantly different compared with controls (p=0.54). New vessels were demonstrated in the subepicardial region.

Conclusions

Autologous mononuclear stem cell therapy was not functionally effective in doxorubicin-induced dilated myocardiopathy in the animal model under study with the experimental conditions, despite occurrence of angiogenic activity.