Abstract 3958: Hepatocyte Growth Factor Mobilises Multipotent Mesoangioblasts
We recently identified clonally expandable, telomerase expressing progenitor cells from peripheral blood of children undergoing cardiopulmonary bypass (CPB) for cardiac surgery. The isolated cells expressed the mesenchymal marker CD73, the endothelial marker KDR, but were negative for the hematopoietic marker CD34 and CD45. The marker profile was distinct from bone marrow-derived hematopoietic or mesenchymal stem cells, but resembled embryonic multipotent mesoangioblasts (MAB). Isolated circulating MAB-like cells (cMABs) from children were capable to differentiate into endothelial cells, smooth muscle cells and cardiomyocytes and improved functional recovery after ischemia in hind limbs and hearts. So far, cMABs had only been obtained during CPB due to ethical reasons. Therefore, we questioned whether circulating cMABs had been mobilized upon the stress induced by CPB and cardioplegia. Indeed, when we used blood from children not undergoing cardiac surgery, the incidence of obtaining clonally expandable MAB-like cells was profoundly reduced (3 out of 10 patients). In order to identify factors involved in the mobilization of cMABs, we screened the profile of circulating cytokines before and after cardiopulmonary bypass in children undergoing open heart surgery. Out of the cytokines tested, hepatocyte growth factor (HGF) was most profoundly up-regulated (2.6 ± 0.2-fold). cMABs abundantly express the HGF receptor, c-Met, and recombinant HGF stimulated the migration of cMABs in vitro (597 ± 30%). Moreover, injection of 1μg/kg HGF in rats significantly increased the number of colonies isolated from the blood (580±191%). The marker profile of the expanded cells was similar to human cMABs. In summary, we identified HGF as a cytokine mediating mobilization of multipotent cMABs into the peripheral blood, which offers the possibility to increase the number of cMABs for therapeutic application.