Abstract 19260: Prothrombotic Activity and Reduction in Coronary Flow Reserve Associated With Therapeutic Intracoronary Delivery of Bone Marrow-Derived Mesenchymal Stem Cells is Ameliorated by Heparin Co-Administration in a Porcine Myocardial Infarction Model

• DOI: 10.1161/circ.128.suppl_22.a19260
• Publication Date: 2024-04-23T10:56:54Z
• Authors: Birgitta M Gleeson; Kenneth Martin; Arun H Kumar; Mohammed T Ali; Frank P Barry; Timothy O’Brien; Noel M Caplice
• Keywords: Coronary flow reserve

Cell therapy remains an evolving therapeutic option for cardiac repair in the case of acute myocardial infarction (AMI) associated with significant cardiomyocyte death. Mesenchymal stem cells (MSCs) are promising candidates promoting salvage post AMI, but concerns regarding safety intracoronary MSC delivery remain. Surface expression tissue factor (TF), a key initiator soluble coagulation cascade, has recently been implicated as possible cause procoagulant activity. This study aimed to characterize prothrombotic activity and identify means managing any thrombotic side effects during AMI. Expression TF on was detected by immunoflourescence, flow cytometry immunoblotting. antigen catalytically active (252.4 ± 8.3 pM/2 x 105 MSC) capable supporting thrombin generation vitro. Addition MSCs whole citrated blood enhanced platelet-driven thrombus deposition collagen at arterial shear (12.67 1.0% untreated vs 18.9 0.9% surface coverage MSC, p>0.001), effect abolished heparin co-administration (p<0.01 alone). Infusion 25 106 via route porcine AMI model decrease coronary reserve when delivered reperfusion (-0.7 0.05) not coadministered (0.1 0.02, p<0.01). Heparin also reduced MSC-associated thrombosis incorporating platelets vWF microvasculature (p<0.05). Therapeutic able reduce apoptosis infarct border zone 24 (p<0.01). Procoagulant is independently reduction perfusion I.C. which may be successfully managed co-administration. highlights important mechanistic insight into