Suspension medium influences interaction of mesenchymal stromal cells with endothelium and pulmonary toxicity after transplantation in mice.
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.
Deak
Erika
E
Stem Cell Biology Group, DRK Institute of Transfusion Medicine and Immune Hematology, Johann Wolfgang Goethe University, D-60528 Frankfurt am Main, Germany.
Rüster
Brigitte
B
Keller
Lisa
L
Eckert
Klaus
K
Fichtner
Iduna
I
Seifried
Erhard
E
Henschler
Reinhard
R
D000818:Animals; D002021:Buffers; D002449:Cell Aggregation / Q000187:drug effects; D002450:Cell Communication / Q000187:drug effects*; D003470:Culture Media / Q000494:pharmacology*; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects*; D006801:Humans; D007275:Injections, Intravenous; D008168:Lung / Q000187:drug effects / Q000473:pathology*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D013314:Stress, Mechanical; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000637:transplantation; D013535:Suspensions
D002021:Buffers; D003470:Culture Media; D013535:Suspensions