Effect of MSCs and MSC-Derived Extracellular Vesicles on Human Blood Coagulation

Abstract

Mesenchymal stem cells (MSCs) have emerged as a potent therapeutic tool for the treatment of a number of pathologies, including immune pathologies. However, unwelcome effects of MSCs on blood coagulation have been reported, motivating us to explore the thrombotic properties of human MSCs from the umbilical cord. We revealed strong procoagulant effects of MSCs on human blood and platelet-free plasma using rotational thromboelastometry and thrombodynamic tests. A similar potentiation of clotting was demonstrated for MSC-derived extracellular vesicles (EVs). To offer approaches to avoid unwanted effects, we studied the impact of a heparin supplement on MSC procoagulative properties. However, MSCs still retained procoagulant activity toward blood from children receiving a therapeutic dose of unfractionated heparin. An analysis of the mechanisms responsible for the procoagulant effect of MSCs/EVs revealed the presence of tissue factor and other proteins involved in coagulation-associated pathways. Also, we found that some MSCs and EVs were positive for annexin V, which implies the presence of phosphatidylserine on their surfaces, which can potentiate clot formation. Thus, we revealed procoagulant activity of MSCs/EVs associated with the presence of phosphatidylserine and tissue factor, which requires further analysis to avoid adverse effects of MSC therapy in patients with a risk of thrombosis.

Procoagulant in vitro effects of clinical cellular therapeutics in a severely injured trauma population

“…To correct the procoagulant effect of AF MSCs in this study, we found that more than double that (12 000 U) was required to normalize the TEG R time. However, a recent study by Silachev et al potentially calls into question the efficacy of heparin treatment to ameliorate the procoagulant effects of CCTs . In their study, blood from newborn infants at high risk of thrombosis was collected 0.5‐1 hour after systemic heparinization at a dose of 5 U/h/kg.…”

Exosomal circular RNA sorting mechanisms and their function in promoting or inhibiting cancer (Review)

“…Numerous studies have confirmed that exosomes act as crucial mediators of intercellular communication (7)(8)(9). In addition, they function in numerous physiological processes, such as blood coagulation (10), tissue repair, skin regeneration (11) and immune modulation (12); therefore, exosomes play roles in cancer and other pathological processes such as in cancer, cerebral ischemia and obesity (13)(14)(15).…”

Mesenchymal stromal cells and their secreted extracellular vesicles as therapeutic tools for COVID-19 pneumonia?

“…On the clinical side, little is known regarding optimal therapeutic doses and optimal route(s) of administration [89]. Regarding safety, MSC-EVs have been shown to exhibit procoagulant activity, similarly to their cells of origin [98], a property that could cause concern in patients prone to thrombotic events such as those with SARS-CoV-2 infection.…”