Article
The reverse remodelling effect of bone-marrow-derived stem cells is independent from the site of epimyocardial cell transplantation
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Published: | May 20, 2011 |
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Introduction: The transplantation of bone-marrow derived stem cells (BMCs) represents a promising therapy in chronic heart failure. Positive effects of transplanting these cells could be shown, but the exact mechanisms are unknown. As paracrine effects are increasingly discussed, we evaluated whether the site of injection effects the potential improvement in LV-contractility and angiogenesis in doxorubicin-induced failing hearts.
Materials and methods: Heart failure was induced in White New Zealand rabbits by doxorubicin (3 mg/kg for 6 weeks), followed by right-ventricular-transplantation (RV-BMC, n=6), left-ventricular-transplantation (LV-BMC, n=6), sham treatment (sham-group, n=6), or no therapy (DOX-group, n=5). Healthy rabbits were used as controls (control-group, n=8). Cells were isolated by bone marrow aspiration and transplanted locally into the ventricular myocardium. Four weeks later cardiac function was assessed and capillary density (CD31-staining) was measured.
Results: Doxyrubicin treatment decreased the ejection fraction (EF) significantly compared to the control-group (DOX-group 29.2±2.6% vs. control-group 44.0±1.6% p=<0.05). There was no statistical difference between sham- and Dox-group. The EF was significant higher in both BMC-groups vs. sham-group (LV-BMC 39.0±1.4% and RV-BMC 39.2±2.6% vs. sham-group 29.8±3.7% p=<0.001), without significance between the BMC-groups (p=0.858). The capillary density (capillaries/high-power-field) increased in both BMC-groups compared to sham-group. The left ventricular injection of BMCs increased the capillary density by 8.3±3.4%, the right ventricular injection by 8.1±2.2% compared to sham-group without significant difference between the two BMC-groups.
Conclusion: The beneficial effects of BMCs transplantation in doxorubicin-induced cardiomyopathy are independent of the injection site. BMCs failed to transdifferentiate into cardiomyocytes. These findings implicate, that paracrine factors are responsible for the beneficial effects of stem cell transplantation.