Editors' ChoiceCELL THERAPY

Cell therapies can bring insult to injury

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Science Translational Medicine  26 Feb 2020:
Vol. 12, Issue 532, eabb0792
DOI: 10.1126/scitranslmed.abb0792

Abstract

Some cell therapies increase the risk of thromboembolism in trauma patients due to high tissue factor expression.

Although mesenchymal stromal cells (MSCs) are often thought of as a uniform cell type, tissue factor (CD142) expression varies widely depending on the source of the cells. Tissue factor activates the coagulation cascade to facilitate blood clot formation. Because CD142 is not routinely used to characterize MSCs, MSCs from different sources can errantly be assumed to have similar safety profiles. Recently, George et al. shed light on the potential thrombotic consequences of introducing MSC therapeutics intravascularly into trauma patients.

The authors compared human MSCs from bone marrow, adipose, and amniotic fluid for their effects on blood clotting. When mixed with blood from healthy donors, all MSC products shortened clotting time. Amniotic MSCs were the most potent, reducing clot formation time from 8 min to just 1.3 min. When repeated with blood from patients with severe trauma, clotting time shortened even further. Severe trauma leads to a hypercoagulable state in which blood clots faster compared with healthy donors. Clotting was further hastened by exposure to cellular therapies, as evidenced by amniotic MSCs’ clotting of blood from trauma patients in under a minute. George et al. went on to show that the procoagulant effect of cell therapies could be reversed with heparin, but the dose of heparin needed to be tailored to the source of the cells. For a typical 80 kg patient, they estimated that the dose of heparin required to prevent coagulation ranged from 240 U for bone marrow MSCs to 12,000 U for amniotic MSCs. This enormous range highlights the need to characterize individual cell therapy products for their procoagulant properties or to engineer them to mask or suppress their tissue factor expression.

Cell therapy is increasingly explored as a treatment for patients experiencing traumatic brain injury and acute lung injury. Although potentially beneficial, this study highlights the challenge of managing coagulation along with cell therapy. Antithrombotic therapy is often withheld from trauma patients immediately after injury due to the risk of uncontrolled bleeding. Thus, the decision to administer cellular therapies in these patients must weigh the potential benefits against the risks of exacerbating either the procoagulant state or uncontrolled bleeding due to antithrombotic therapy.

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