Bone marrow-derived mononuclear cell seeded bioresorbable vascular graft improves acute graft patency by inhibiting thrombus formation via platelet adhesion

Background: Acute thrombosis is a crucial cause of bioresorbable vascular graft (BVG) failure. Bone marrow-derived mononuclear cell (BM-MNC)-seeded BVGs demonstrated high graft patency, however, the effect of seeded BM-MNCs against thrombosis remains to be elucidated. Thus, we evaluated an antithrombotic effect of BM-MNC-seeding and utilized platelet-depletionmousemodels to evaluate the contribution of platelets to acute thrombosis of BVGs. Methods and results: BVGs were composed of poly(glycolic acid) mesh sealed with poly(L-lactideco-ε- caprolactone). BM-MNC-seeded BVGs and unseeded BVGs were implanted to wild type C57BL/6 mice (n=10/group) as inferior vena cava interposition conduits. To evaluate platelet effect on acute thrombosis, c-Mpl−/− mice and Pf4-Cre+; iDTR mice with decreased platelet number were also implanted with unseeded BVGs (n=10/group). BVG patency was evaluated at 2, 4, and 8 weeks by ultrasound. BM-MNC-seeded BVGs demonstrated a significantly higher patency rate than unseeded BVGs during the acute phase (2-week, 90% vs 30%, p=.020), and patency rates of these grafts were sustained until week 8. Similar to BM-MNC-seeded BVGs, C-Mpl−/−and Pf4-Cre+; iDTRmice also showed favorable graft patency (2-week, 90% and 80%, respectively) during the acute phase. However, the patency rate of Pf4-Cre+; iDTRmice decreased gradually after DTR treatment as plateletnumberrecovered tobaseline.Anin vitro studyrevealedBM-MNC-seeding significantly inhibitedplatelet adhesion to BVGs compared to unseeded BVGs, (1.75±0.45 vs 8.69±0.68×103 platelets/mm2,p b .001). Conclusions:BM-MNC-seeding and the reduction in platelet number prevented BVG thrombosis and improved BVG patency, and those resultsmight be caused by inhibiting platelet adhesion to the BVG.