Bone marrow-derived mononuclear cell seeded bioresorbable vascular graft improves acute graft patency by inhibiting thrombus formation via platelet adhesion
Bone marrow-derived mononuclear cell seeded bioresorbable vascular graft improves acute graft patency by inhibiting thrombus formation via platelet adhesion
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DOI：
10.1016/j.ijcard.2018.01.059
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发表时间：
2018-09-01
影响因子：
3.5
通讯作者：
Shinoka, Toshiharu
中科院分区：
文献类型：
--
作者：
Miyachi, Hideki;Reinhardt, James W.;Shinoka, Toshiharu
背景：急性血栓形成是生物可吸收血管移植（BVG）失败的重要原因。骨髓源性单核细胞（BM-MNC）种子BVGs具有较高的移植物通畅性，然而，种子BM-MNC对血栓形成的影响仍有待阐明。因此，我们评估了bm - mnc种子的抗血栓作用，并利用血小板耗尽小鼠模型来评估血小板对bvg急性血栓形成的贡献。方法与结果：采用聚l -乳酸deco-乙己内酯密封的聚乙醇酸网状结构制备bvg。以野生型C57BL/6小鼠（n = 10/组）作为下腔静脉介入导管，分别植入bm - mnc种子bvg和未种子bvg。评价血小板对急性血栓形成、c-Mpl（-/-）小鼠和Pf4-Cre（+）的影响；血小板数量减少的iDTR小鼠同时植入未播种的bvg （n = 10/组）。分别于2、4、8周超声检查BVG通畅程度。在急性期（2周，90% vs 30%, p = 0.020）， bm - mnc移植的BVGs的通畅率明显高于未播种的BVGs，并且这些移植物的通畅率持续到第8周。类似于bm - mnc种子bvg， C-Mpl（-/-）和Pf4-Cre(+)；iDTR小鼠在急性期也表现出良好的移植物通畅（2周，分别为90%和80%）。然而，Pf4-Cre的通畅率（+）；DTR治疗后iDTR小鼠随着血小板数量恢复到基线水平逐渐下降。一项体外研究显示，与未播种的bvg相比，bm - mnc播种显著抑制了血小板对bvg的粘附(1.75 +/- 0.45 vs 8.69 +/- 0.68 × 10（3)个血小板/mm(2), p < .001）。结论：bm - mnc播种术及血小板数量减少可预防BVG血栓形成，改善BVG通畅，其作用可能与抑制血小板粘附BVG有关。(c) 2018年作者。这是一篇基于CC by - nc - nd许可的开放获取文章。
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.