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

INTERNATIONAL JOURNAL OF CARDIOLOGY

卷:266

Article

Miyachi, Hideki^1,2,3  Reinhardt, James W.^1,2  Otsuru, Satoru⁴  Tara, Shuhei^1,2,3  Nakayama, Hidetaka⁵  Yi, Tai^1,2  Lee, Yong-Ung^1,2  Miyamoto, Shinka^1,2  Shoji, Toshihiro^1,2  Sugiura, Tadahisa^1,2  Breuer, Christopher K.^1,2  Shinoka, Toshiharu^1,2,6 

[1] Nationwide Childrens Hosp, Res Inst, Tissue Engn Program, Columbus, OH USA

[2] Nationwide Childrens Hosp, Res Inst, Ctr Cardiovasc & Pulm Res, Columbus, OH USA

[3] Nippon Med Sch, Dept Cardiovasc Med, Tokyo, Japan

[4] Nationwide Childrens Hosp, Res Inst, Ctr Childhood Canc & Blood Dis, Colurnbus, OH USA

[5] Gunze Ltd, QOL Res Ctr Lab, Ayabe, Kyoto, Japan

[6] Nationwide Childrens Hosp, Ctr Heart, Dept Cardiothorac Surg, 700 Childrens Dr,T2294, Columbus, OH 43205 USA

关键词: Platelet;    Anticoagulation;    Thrombosis;    Mononuclear cell;    Patency;   

DOI  :  10.1016/j.ijcard.2018.01.059

来源: Elsevier

【 摘 要 】

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-depletion mouse models 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-ecaprolactone). 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(+); iDTR mice also showed favorable graft patency (2-week, 90% and 80%, respectively) during the acute phase. However, the patency rate of Pf4-Cre(+); iDTR mice decreased gradually after DTR treatment as platelet number recovered to baseline. An in vitro study revealed BM-MNC-seeding significantly inhibited platelet adhesion to BVGs compared to unseeded BVGs, (1.75 +/- 0.45 vs 8.69 +/- 0.68 x 10(3) platelets/mm(2), p < .001). Conclusions: BM-MNC-seeding and the reduction in platelet number prevented BVG thrombosis and improved BVG patency, and those results might be caused by inhibiting platelet adhesion to the BVG. (c) 2018 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license.

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