Abstract 3470: Acute Myocardial Infarction Activates Progenitor Cells in the Bone Marrow of Patients with Coronary Artery Disease

Abstract

Background: Bone marrow - derived progenitor cells (BMC) may contribute as an endogenous repair mechanism to the recovery of left ventricular function after acute myocardial infarction (AMI). So far, however, there are no clinical data demonstrating alterations in the bone marrow (BM) niche after AMI, which may have an impact on the composition and functional activity of BM-resident progenitor cells.

Results: Initial studies using FDG-PET imaging revealed a significantly increased metabolic activity within the BM of patients (pts) with AMI compared to pts with healed (> 3 months old) myocardial infarction. Moreover, infusion of ex-vivo Indium-111 labelled progenitor cells revealed a significantly enhanced re-uptake into the BM in pts with AMI (N=8, 0.3±0.09 % of overall radioactivity) compared to pts with healed myocardial infarction (N=6, 0.1±0.01 %, p=0.029 vs. AMI), demonstrating activation of the BM in pts with AMI. In order to more precisely characterize alterations in the composition and functional activity of progenitor cells within the BM of patients with AMI, we analyzed BMC of 204 patients undergoing BM aspiration within 1 to 8 days after AMI. The overall number of mononuclear cells within the BM did not change over time after AMI. In contrast, however, there was a significant increase in the percentage of CD34⁺ (p=0.01) and CD133⁺ (p=0.006) progenitor cells, but not in hematopoietic colony forming capacity (p=0.43) over time. More importantly, functional activity as assessed by migratory capacity of mononuclear cells towards the chemoattractant SDF-1 was significantly (p=0.03) increased from day 1 to day 8 after AMI.

Conclusion: AMI is associated with activation of progenitor cells within the BM, as evidenced by increased metabolic activity of the BM, enhanced re-uptake of infused progenitor cells into the BM as well as upregulation of functional activity and progenitor cell characteristics of BMC within days after AMI. These findings, for the first time, document activation of the stem cell niche within the BM following AMI, which may have important implications for the optimal timing of cell therapy using BMC in patients with AMI.