Abstract 9122: Heparin Mobilizes Multipotent Human Mesoangioblasts

Abstract

The identification of clinically applicable drugs which mobilize endogenous mesenchymal progenitor cells may offer novel therapeutic application in cardiovascular diseases. We recently showed that hepatocyte growth factor (HGF) induces the mobilization of multipotent circulating mesenchymal cells that co-express endothelial markers (so-called circulating mesoangioblasts, cMABs). Since HGF only has a short half life, we investigated whether heparin might be useful to endogenously increase HGF levels thereby inducing the mobilization of cMABs. Heparin was infused in patients with coronary artery disease at a concentration of 200 U/kg (n=11 patients) and 300 U/kg (n=11 patients) and serum HGF levels were determined by ELISA. Consistent with published studies, heparin dose-dependently increased HGF levels to 34.4+1.9 in patients receiving 200U/kg heparin and 42.8+0.9 ng/ml in the patients treated with 300 U/kg. Moreover, heparin dose-dependently increased the number of circulating mesenchymal cell colonies. Patients receiving 200U/kg showed 0.30+0.12 colonies / mononuclear cells (x10 6 ). Further increasing the heparin dosage to 300U/kg increased the number of colonies to 0.63+0.17 colonies / mononuclear cells (x10 6 ). In contrast, we were never able to obtain colonies in patients receiving heparin concentrations below 100 U/kg. The mesenchymal origin of the colonies was characterised by the lack of hematopoietic progenitor cell markers CD45 and CD34. Consistent with the original characterisation of the mesoangioblasts, the colonies expressed the mesenchymal marker CD73, the HGF-receptor c-Met as well as the endothelial marker KDR. In conclusion, we demonstrate that heparin can dose-dependently mobilize mesenchymal progenitor cells in humans. These findings might open up an avenue to non-invasively obtain multipotent mesenchymal cells for therapeutic application in patients with cardiovascular disease.