Abstract
Intravenous (i.v.) transplantation and subsequent homing of Mesenchymal Stromal Cells (MSC) may be adversely influenced by their relatively high adhesion capacity and their tendency to aggregate, leading to clogging of capillaries especially in the lungs. We evaluated the ability of murine MSC suspended in EDTA or heparin in buffered saline solution on their spontaneous adhesion to endothelial cells in vitro, under shear stress and their in vivo tolerability after i.v. injection. We show that suspension of MSC in heparin was highly beneficial, avoiding clinical symptoms in 95% of mice, whereas application of MSC suspended in PBS/EDTA or control buffer caused severe pulmonary reactions and partly, death. In vitro studies using parallel plate flow chambers revealed increased adhesion of MSC suspended in PBS/EDTA to endothelial cells compared with MSC in PBS/heparin. These data provide a means to predict and to interfere with toxicity of i.v. transplanted MSC.
Acknowledgment
We gratefully acknowledge the excellent technical help of Sabrina Böhme and Victoria Lang. This work has been financially supported through the German Ministry of Education and Research (BMBF, Grant No. 01GN0592), DFG Excellence Cluster Cardio-pulmonary Systems (ECCPS) and the EU Project CASCADE.
Disclosure of interest: None of the authors has potential conflicts of interest to disclose.