Abstract 16941: Differentially Secreted MicroRNAs of Bone Marrow-Derived Mononuclear Cells Might Influence Cardiovascular Repair After Acute Ischemia
Initial trials as well as meta-analyses suggest that bone marrow-derived mononuclear cells (BMC) augment neovascularization after ischemia. Due to the low engraftment of BMC into the heart, paracrine factors are thought to be responsible for the improvement after cell therapy after acute ischemia. Recent studies demonstrated that cells release microRNA (miR) that can be taken up and regulate target gene expression in other cells. The aim of our study was to determine the secretion of miRs by BMC used to activate cardiovascular repair. BMC were isolated from bone marrow aspirates obtained from patients with CAD (CAD-BMC, n=7) or healthy volunteers (HC-BMC, n=14). The five potentially angiogenesis-regulating miRs, miR-17, -29c, -92a, -126, and -150 were measured in BMC as well as in their secretome by qPCR. The cellular levels of miR-17, -29c, and -126 did not differ between BMC derived from HC versus CAD-patients. However, miR-92a and miR-150 were significantly reduced in CAD-BMC compared to HC-BMC (58±61% and 31±32% of HC-BMC, p<0.05 respectively). MiRs-17, -29c, -126 and -150 were also detected at similar levels in the secretome (whole supernatant (SN) as well as microvesicles (MV) isolated by ultra-centrifugation) of HC-BMC and CAD-BMC. However, CAD-BMC secreted significant higher levels of miR-92a compared to HC-BMC (235±195% of HC-BMC, p<0.05). By calculating the copy number of miRs in the cells as well as in the supernatant, we detected an increase of approximately 500% in secretion of miR-92a by CAD-BMC. This study demonstrates that BMC secrete different angiogenes-regulating miRs. MiR-92a is efficiently secreted by CAD-BMC. The increased secretion of the anti-angiogenic miR-92a in patient-derived BMC might partly explain the lower regeneration potential of CAD-BMC compared to HC-BMC. Interferences with miR expression as well as potentially secretion might be promising tools to increase the therapeutic potential of BMC for cardiovascular repair.
- © 2012 by American Heart Association, Inc.