Department of Biomedical Engineering, University at Buffalo, State University of New York, Amherst, NY, 14260, USA.
Department of Chemical and Biological, University at Buffalo, State University of New York, Amherst, NY, 14260, USA.
Nat Commun. 2020 Apr 1;11(1):1622. doi: 10.1038/s41467-020-15361-2.
Recently our group demonstrated that acellular tissue engineered vessels (A-TEVs) comprised of small intestinal submucosa (SIS) immobilized with heparin and vascular endothelial growth factor (VEGF) could be implanted into the arterial system of a pre-clinical ovine animal model, where they endothelialized within one month and remained patent. Here we report that immobilized VEGF captures blood circulating monocytes (MC) with high specificity under a range of shear stresses. Adherent MC differentiate into a mixed endothelial (EC) and macrophage (Mφ) phenotype and further develop into mature EC that align in the direction of flow and produce nitric oxide under high shear stress. In-vivo, newly recruited cells on the vascular lumen express MC markers and at later times they co-express MC and EC-specific proteins and maintain graft patency. This novel finding indicates that the highly prevalent circulating MC contribute directly to the endothelialization of acellular vascular grafts under the right chemical and biomechanical cues.
最近，我们的研究小组证明，由肝素和血管内皮生长因子（VEGF）固定化的小肠黏膜下层（SIS）组成的去细胞组织工程血管（A-TEV）可以植入临床前绵羊动物模型的动脉系统中，在一个月内内皮化并保持通畅。在这里，我们报告说，在一定的剪切力范围内，固定化的 VEGF 可以特异性地捕获循环中的单核细胞（MC）。附着的 MC 分化为混合的内皮细胞（EC）和巨噬细胞（Mφ）表型，并进一步发育为成熟的 EC，在高剪切力下沿血流方向排列并产生一氧化氮。在体内，血管腔表面新募集的细胞表达 MC 标志物，而在稍后的时间，它们共同表达 MC 和 EC 特异性蛋白，并保持移植物通畅。这一新颖的发现表明，在适当的化学和生物力学线索下，高度流行的循环 MC 直接有助于去细胞血管移植物的内皮化。
