effect of heparin on the biological properties and molecular signature of human mesenchymal stem cells chronic use of heparin as an anticoagulant for the treatment of thrombosis or embolism invokes many adverse systemic events including thrombocytopenia vascular reactions and osteoporosis here we addressed whether adverse effects might also be directed to mesenchymal stem cells that reside in the bone marrow compartment harvested human bone marrowderived mesenchymal stem cells hmscs were exposed to varying doses of heparin and their responses profiled at low doses 200 ngml serial passaging with heparin exerted a variable effect on hmsc proliferation and multipotentiality across multiple donors while at higher doses 100 gml heparin supplementation inhibited cell growth and increased both senescence and cell size gene expression profiling using cdna arrays and rnaseq analysis revealed pleiotropic effects of lowdose heparin on signaling pathways essential to hmsc growth and differentiation including the tgfbmp superfamily fgfs and wnts cells serially passaged in lowdose heparin possess a donordependent gene signature that reflects their altered phenotype our data indicate that heparin supplementation during the culturing of hmscs can alter their biological properties even at low doses this warrants caution in the application of heparin as a culture supplement for the ex vivo expansion of hmscs it also highlights the need for careful evaluation of the bone marrow compartment in patients receiving chronic heparin treatment