Antithrombogenic property of bone marrow mesenchymal stem cells in nanofibrous vascular grafts
Antithrombogenic property of bone marrow mesenchymal stem cells in nanofibrous vascular grafts
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DOI：
10.1073/pnas.0704581104
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发表时间：
2007-07-17
影响因子：
11.1
通讯作者：
Li, Song
中科院分区：
文献类型：
--
作者：
Hashi, Craig K.;Zhu, Yiqian;Li, Song
纳米结构生物材料在组织工程中具有巨大的应用潜力。然而，纳米材料在体内的性能和整合还没有很好的理解。血管组织工程的一个挑战是开发最佳的支架，并建立可膨胀的细胞来源，用于构建组织工程血管移植物，这些血管移植物是非血栓形成的，具有长期通畅性。在这里，我们使用组织工程血管移植物作为模型，以证明结合纳米纤维支架和骨髓间充质干细胞（MSC）的血管组织工程的潜力。具有对齐的纳米纤维的可生物降解的纳米纤维支架用于模拟天然胶原原纤维以引导血管移植物中的细胞组织。动脉旁路实验的结果表明，纳米纤维支架允许血管细胞的有效浸润和基质重塑。无细胞移植物（无间充质干细胞）导致显著的内膜增厚，而细胞移植物（有间充质干细胞）具有良好的长期通畅性，并表现出良好的组织层的内皮细胞（EC）和平滑肌细胞（SMC），在天然动脉。短期实验表明，纳米纤维支架单独诱导血小板粘附和血栓形成，这是抑制MSC接种。此外，骨髓间充质干细胞作为内皮细胞，在体外抗血小板粘附，这依赖于细胞表面的硫酸乙酰肝素蛋白多糖。这些数据以及对MSC短期植入的观察表明，细胞移植物的长期通畅性可能归因于MSC的抗血栓形成特性。这些结果证明了纳米纤维支架的几个有利特征，小直径纳米纤维血管移植物的良好通畅性，以及MSC独特的抗血栓形成特性。
Nanostructured biomaterials have tremendous potential for tissue engineering. However, the performance and integration of the nanornaterials in vivo are not well understood. A challenge in vascular tissue engineering is to develop optimal scaffolds and establish expandable cell sources for the construction of tissue-engineered vascular grafts that are nonthrombogenic and have long-term patency. Here, we used tissue-engineered vascular grafts as a model to demonstrate the potential of combining nanofibrous scaffolds and bone marrow mesenchymal stem cells (MSCs) for vascular tissue engineering. Biodegradable nanofibrous scaffolds with aligned nanofibers were used to mimic native collagen fibrils to guide cell organization in vascular grafts. The results from artery bypass experiments showed that nanofibrous scaffolds allowed efficient infiltration of vascular cells and matrix remodeling. Acellular grafts (without MSCs) resulted in significant intimal thickening, whereas cellular grafts (with MSCs) had excellent long-term patency and exhibited well organized layers of endothelial cells (ECs) and smooth muscle cells (SMCs), as in native arteries. Short-term experiments showed that nanofibrous scaffolds alone induced platelet adhesion and thrombus formation, which was suppressed by MSC seeding. In addition, MSCs, as ECs, resisted platelet adhesion in vitro, which depended on cell-surface heparan sulfate proteoglycans. These data, together with the observation on the short-term engraftment of MSCs, suggest that the long-term patency of cellular grafts may be attributed to the antithrombogenic property of MSCs. These results demonstrate several favorable characteristics of nanofibrous scaffolds, the excellent patency of small-diameter nanofibrous vascular grafts, and the unique antithrombogenic property of MSCs.