Vascular mimicry has been thoroughly investigated in tumor angiogenesis. In this study, we demonstrate for the first time that a process closely resembling tumor vascular mimicry is present during physiological blood vessel formation in tissue regeneration using the zebrafish fin regeneration assay. At the fin-regenerating front, vasculature is formed by mosaic blood vessels with endothelial-like cells possessing the morphological phenotype of a macrophage and co-expressing both endothelial and macrophage markers within single cells. Our data demonstrate that the vascular segments of the regenerating tissue expand, in part, through the transformation of adjacent macrophages into endothelial-like cells, forming functional, perfused channels and contributing to the de novo formation of microvasculature. Inhibiting the formation of tubular vascular-like structures by CVM-1118 prevents vascular mimicry and network formation resulting in a 70% shorter regeneration area with 60% reduced vessel growth and a complete absence of any signs of regeneration in half of the fin area. Additionally, this is associated with a significant reduction in macrophages. Furthermore, depleting macrophages using macrophage inhibitor PLX-3397, results in impaired tissue regeneration and blood vessel formation, namely a reduction in the regeneration area and vessel network by 75% in comparison to controls.

血管拟态在肿瘤血管生成中已得到彻底研究。在这项研究中，我们首次使用斑马鱼鳍再生测定证明，在组织再生的生理血管形成过程中存在与肿瘤血管拟态非常相似的过程。在鳍再生前端，脉管系统由镶嵌血管和内皮样细胞形成，内皮样细胞具有巨噬细胞的形态表型，并在单细胞内共表达内皮细胞和巨噬细胞标记。我们的数据表明，再生组织的血管部分扩张，部分是通过邻近的巨噬细胞转化为内皮样细胞，形成功能性的、灌注的通道，并有助于微血管系统的从头形成。通过 CVM-1118 抑制管状血管样结构的形成，可防止血管拟态和网络形成，导致再生区域缩短 70%，血管生长减少 60%，并且一半鳍区域完全没有任何再生迹象。此外，这与巨噬细胞的显着减少有关。此外，使用巨噬细胞抑制剂 PLX-3397 消耗巨噬细胞会导致组织再生和血管形成受损，即与对照组相比，再生面积和血管网络减少 75%。