Abstract 2041: Transplantation of Bone Marrow Cells, but not Skeletal Myoblasts, Normalizes the Downregulation of Myocardial Akt in Chronic Heart Failure
Background: Transplantation of bone marrow cells (BMC) or skeletal myoblasts (SMB) has been proposed as a potential therapy for treating heart failure. The mechanism of the therapeutic effect is not understood, but recent evidence suggestes that paracrine effects may play an important role. In this study, we investigated whether the paracrine effect is affected by donor cell type and cell-delivery route.
Methods and Results: Female rats underwent injection of either 5×106 male SMB, 10×106 male mononuclear BMC or PBS via either intramyocardial (IM) or retrograde intracoronary (IC) route at 3 weeks after left coronary artery occlusion. Every type of cell transplantation demonstrated an improved LVEF compared to PBS injection at 28 days. Quantitative PCR for the male-specific Sry gene showed that the graft size was not different between groups at any time points. Using real time PCR we examined the changes in expression of more than 20 genes that were presumed to be involved in the paracrine effect. Most interestingly, Akt was down regulated at 3 and 7 days in all groups, while this downregulation was fully normalised by 28 days in both IM and IC injection of BMC, but not SMB (Table⇓). Pro-inflammatory cytokines including IL-1β and IL-6 were markedly upregulated at 3 and 7 day of both types of SMB injection compared to BMC injection. Although this upregulation had mostly receded by 28 days, this marked increase in pro-inflammatory cytokines may be the underlying cause for SMB not being able to recover to normal Akt levels. Expression of cardiothorophin, JAK1 or STAT3 was not affected by any types of cell transplantation compared to PBS injection. HIF-1α was upregulated after transplantation of SMB, but not BMC.
Conclusion: Transplantation of bone marrow cells, but not skeletal myoblasts, normalizes the down regulation of Akt in post-infarction chronic heart failure, regardless of the delivery route, suggesting some components of paracrine effect may be specific to the cell-type.