Tissue factor related thrombogenesis induced by heterologous human adult liver-derived progenitor cell infusion : modulation by cell dose escalation and anticoagulant drugs : clinical application and relevance

Abstract

Mesenchymal stem cells (MSCs) are used in numerous clinical trials nowadays, but their blood compatibility is still an important concern. MSCs express a procoagulant activity, linked to the expression of tissue factor (TF), leading to thrombi formation after blood exposure. However, different approaches could be useful to prevent these side effects. In this thesis, we demonstrated that TF, known to be expressed by liver-derived MSCs, induces in a cell dose dependent manner, the activation of coagulation, resulting in fibrin generation and platelet activation. Thrombogenic adverse events induced by MSCs infusions could either be prevented by using low cell doses (5 × 106 cells/kg) or high cell doses (50 × 106 cells/kg) combined with anticoagulant drugs. Next, we also observed that activation of coagulation by liver-derived MSCs is less strong in blood from acute decompensated patients compared to healthy control subjects. Finally, during a clinical trial on eleven patients presenting with metabolic liver disorders, we showed that adding anticoagulant drugs during cell infusions is safe and limits infusion related thrombogenesis to subclinical signs in most of the patients.(MED - Sciences médicales) -- UCL, 202