Diaz-Santana Anthony, Shan Mengrou, Stroock Abraham D
School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, New York, USA.
Integr Biol (Camb). 2015 Apr;7(4):454-66. doi: 10.1039/c5ib00052a.
Vascular anastomosis - the fusion of vessels from two distinct branches of the vascular system - represents a critical step in vascular growth under both healthy and pathological conditions, in vivo, and presents an important target for engineering of vascularized tissues, in vitro. Recent works in animal models have advanced our understanding of the molecular and cellular players in vascular anastomosis, but questions remain related to cellular dynamics and control of this process, in vitro. In this study, we exploited a three-dimensional (3-D) culture platform to examine the dynamics of endothelial cell (EC) during and after vascular anastomosis by allowing angiogenesis and vasculogenesis to proceed in parallel. We show that anastomosis occurs between sprouts formed by angiogenesis from an endothelium and tubes formed by vasculogenesis in the bulk of a 3-D matrix. This fusion leads to highly connected vessels that span from the surface of the matrix into the bulk in a manner that depends on cell density and identity. Further, we observe and analyze intermixing of endothelial cells of distinct origin (surface versus bulk) within the vessels structures that are formed; we provide evidence that the cells migrate along pre-existing vessels segments as part of this intermixing process. We conclude that anastomosis can occur between vessels emerging by angiogenesis and vasculogenesis and that this process may play an important role in contexts such as wound healing.
血管吻合——来自血管系统两个不同分支的血管融合——在体内健康和病理条件下的血管生长中都是关键步骤，并且在体外是血管化组织工程的重要靶点。动物模型的最新研究进展加深了我们对血管吻合中分子和细胞作用的理解，但在体外，关于该过程的细胞动力学和控制仍存在问题。在本研究中，我们利用三维（3-D）培养平台，通过使血管生成和血管发生并行进行，来研究血管吻合期间及之后内皮细胞（EC）的动力学。我们发现，血管吻合发生在内皮细胞血管生成形成的芽与三维基质主体中血管发生形成的管之间。这种融合形成高度连通的血管，其以依赖于细胞密度和特性的方式从基质表面延伸至主体内部。此外，我们观察并分析了在形成的血管结构中不同来源（表面与主体）内皮细胞的混合情况；我们提供证据表明，作为这种混合过程的一部分，细胞沿着预先存在的血管段迁移。我们得出结论，血管生成和血管发生产生的血管之间可发生吻合，并且该过程可能在伤口愈合等情况中发挥重要作用。
