Modeling angiogenesis in the human brain in a tissue-engineered post-capillary venule

IF 9.2 1区 医学 Q1 PERIPHERAL VASCULAR DISEASE
Nan Zhao, Sarah Kulkarni, Sophia Zhang, Raleigh M. Linville, Tracy D. Chung, Zhaobin Guo, John J. Jamieson, Danielle Norman, Lily Liang, Alexander F. Pessell, Peter Searson
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引用次数: 4

Abstract

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.

Abstract Image

组织工程化毛细血管后微静脉中人脑血管生成的建模
血管生成在胚胎发育、器官重塑、伤口愈合中发挥着重要作用,也与许多人类疾病有关。在动物模型中,大脑发育过程中的血管生成过程得到了很好的表征,但对成熟大脑中的血管形成过程知之甚少。在这里,我们使用组织工程后毛细血管微静脉(PCV)模型,结合干细胞诱导的脑微血管内皮样细胞(iBMECs)和周细胞样细胞(iPCs)来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。我们发现iBMECs和iPCs都可以作为引导血管生成芽的尖端细胞。更重要的是,iPC引导的芽的生长速率比iBMEC引导的芽高出大约两倍。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方向偏差。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生长。
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来源期刊
Angiogenesis
Angiogenesis PERIPHERAL VASCULAR DISEASE-
CiteScore
21.90
自引率
8.20%
发文量
37
审稿时长
6-12 weeks
期刊介绍: Angiogenesis, a renowned international journal, seeks to publish high-quality original articles and reviews on the cellular and molecular mechanisms governing angiogenesis in both normal and pathological conditions. By serving as a primary platform for swift communication within the field of angiogenesis research, this multidisciplinary journal showcases pioneering experimental studies utilizing molecular techniques, in vitro methods, animal models, and clinical investigations into angiogenic diseases. Furthermore, Angiogenesis sheds light on cutting-edge therapeutic strategies for promoting or inhibiting angiogenesis, while also highlighting fresh markers and techniques for disease diagnosis and prognosis.
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