Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, 21218, USA.
Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA.
Angiogenesis. 2023 May;26(2):203-216. doi: 10.1007/s10456-023-09868-7. Epub 2023 Feb 16.
Angiogenesis plays an essential role in embryonic development, organ remodeling, wound healing, and is also associated with many human diseases. The process of angiogenesis in the brain during development is well characterized in animal models, but little is known about the process in the mature brain. Here, we use a tissue-engineered post-capillary venule (PCV) model incorporating stem cell derived induced brain microvascular endothelial-like cells (iBMECs) and pericyte-like cells (iPCs) to visualize the dynamics of angiogenesis. We compare angiogenesis under two conditions: in response to perfusion of growth factors and in the presence of an external concentration gradient. We show that both iBMECs and iPCs can serve as tip cells leading angiogenic sprouts. More importantly, the growth rate for iPC-led sprouts is about twofold higher than for iBMEC-led sprouts. Under a concentration gradient, angiogenic sprouts show a small directional bias toward the high growth factor concentration. Overall, pericytes exhibited a broad range of behavior, including maintaining quiescence, co-migrating with endothelial cells in sprouts, or leading sprout growth as tip cells.
血管生成在胚胎发育、器官重塑、伤口愈合中起着至关重要的作用，也与许多人类疾病有关。在动物模型中，人们对发育过程中大脑中的血管生成过程有了很好的描述，但对成熟大脑中的这一过程知之甚少。在这里，我们使用一种组织工程化的毛细血管后静脉（PCV）模型，其中包含干细胞衍生的诱导性脑微血管内皮样细胞（iBMEC）和周细胞样细胞（iPC），以可视化血管生成的动力学。我们比较了两种条件下的血管生成：对生长因子灌注的反应和存在外部浓度梯度的情况下。我们表明，iBMEC 和 iPC 都可以作为引导血管生成芽的尖端细胞。更重要的是，iPC 引导的芽的生长速度比 iBMEC 引导的芽快约两倍。在浓度梯度下，血管生成芽表现出向高生长因子浓度的小的定向偏差。总的来说，周细胞表现出广泛的行为，包括保持静止、与芽中的内皮细胞共同迁移，或作为尖端细胞引导芽的生长。
