Abstract
Mesenchymal stem cells (MSCs) are currently studied and used in numerous clinical trials. Nevertheless, some concerns have been raised regarding the safety of these infusions and the thrombogenic risk they induce. MSCs express procoagulant activity (PCA) linked to the expression of tissue factor (TF) that, when in contact with blood, initiates coagulation. Some even describe a dual activation of both the coagulation and the complement pathway, called Instant Blood-Mediated Inflammatory Reaction (IBMIR), explaining the disappointing results and low engraftment rates in clinical trials. However, nowadays, different approaches to modulate the PCA of MSCs and thus control the thrombogenic risk after cell infusion are being studied. This review summarizes both in vitro and in vivo studies on the PCA of MSC of various origins. It further emphasizes the crucial role of TF linked to the PCA of MSCs. Furthermore, optimization of MSC therapy protocols using different methods to control the PCA of MSCs are described.
Highlights
Solid organ transplantation is still the treatment of choice for patients presenting end-stage organ disease
Stéphenne et al [61] described that both isolated human adult liver-derived mesenchymal progenitor cells and bone marrow mesenchymal stem cells (BMMSCs) exhibited significantly measurable procoagulant activity (PCA) by thromboelastometry
Described that both BMMSCs and placenta-derived decidual stromal cells (DSCs) express a PCA linked to the expression of tissue factor (TF), inducing, in a whole-blood Chandler tubing model, a decrease in platelets and the formation of thrombin
Summary
Solid organ transplantation is still the treatment of choice for patients presenting end-stage organ disease. Due to organ shortage, the growing demand for organs and the substantial risks of morbidity and mortality linked to immunosuppression and surgery, other treatments, such as cell-based therapy, are being developed. Activation of coagulation has been reported in several transplanted patients [3,4,5,6,7,8], and could be linked to tissue factor (TF) expression. We discuss current knowledge about the interaction between transplanted cells and blood, . Cells 2019, 8, 1160 focusing on the thrombogenic risk induced by MSCs. We discuss the link between coagulation and inflammation through the IBMIR. We review the different methods that groups investigated to modulate this thrombogenic risk and improve MSCs therapy
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