Physicochemical regulation of endothelial sprouting in a 3D microfluidic angiogenesis model.
Physicochemical regulation of endothelial sprouting in a 3D microfluidic angiogenesis model.
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3D微流血管生成模型中内皮发芽的物理化学调节。
DOI：
10.1002/jbm.a.34587
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发表时间：
2013-10
影响因子：
4.9
通讯作者：
Fischbach, Claudia
中科院分区：
文献类型：
--
作者：
Verbridge, Scott S.;Chakrabarti, Anirikh;DelNero, Peter;Kwee, Brian;Varner, Jeffrey D.;Stroock, Abraham D.;Fischbach, Claudia
生理和病理组织重塑（例如，分别在伤口愈合和癌症期间）需要通过血管生成形成新的血管，但部分由于缺乏生物学相关的体外模型，潜在的微环境机制仍然定义不清。在这里，我们提出了一个基于生物材料的微流控3-D平台，用于分析内皮发芽响应形态梯度。该系统由嵌入I型胶原水凝胶中的三个光刻限定的通道组成。中央通道被内皮细胞包被，两个平行的侧通道作为生物化学梯度稳态产生的源和汇。血管内皮生长因子（VEGF）的前体促进发芽，从而内皮细胞的反应性显着依赖于细胞密度和血管几何形状，无论治疗条件。这些结果指向机械和/或自分泌机制，可能压倒促血管生成旁分泌信号在某些条件下。迄今为止，几何效应和细胞密度都没有被认为是健康和疾病中血管生成的关键决定因素。这种仿生血管平台被证明可用于描绘迄今为止未被充分认识的血管生成贡献者，未来的研究可能会实现重要的新机制见解，这将为抗血管生成癌症治疗提供信息。
Both physiological and pathological tissue remodeling (e.g., during wound healing and cancer, respectively) require new blood vessel formation via angiogenesis, but the underlying microenvironmental mechanisms remain poorly defined due in part to the lack of biologically relevant in vitro models. Here, we present a biomaterials-based microfluidic 3-D platform for analysis of endothelial sprouting in response to morphogen gradients. This system consists of three lithographically defined channels embedded in type I collagen hydrogels. A central channel is coated with endothelial cells, and two parallel side channels serve as a source and a sink for the steady-state generation of biochemical gradients. Gradients of vascular endothelial growth factor (VEGF) promoted sprouting, whereby endothelial cell responsiveness was markedly dependent on cell density and vessel geometry regardless of treatment conditions. These results point toward mechanical and/or autocrine mechanisms that may overwhelm pro-angiogenic paracrine signaling under certain conditions. To date, neither geometrical effects nor cell density have been considered critical determinants of angiogenesis in health and disease. This biomimetic vessel platform demonstrated utility for delineating hitherto underappreciated contributors of angiogenesis, and future studies may enable important new mechanistic insights that will inform anti-angiogenic cancer therapy.
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影响因子：
64.8
作者：
Mammoto, Akiko;Connor, Kip M.;Mammoto, Tadanori;Yung, Chong Wing;Huh, Dongeun;Aderman, Christopher M.;Mostoslavsky, Gustavo;Smith, Lois E. H.;Ingber, Donald E.
通讯作者：
Ingber, Donald E.
影响因子：
82.9
作者：
Mizukami, Y;Jo, WS;Chung, DC
通讯作者：
Chung, DC
影响因子：
41.2
作者：
通讯作者：
--
分子机制和血管生成的临床应用。
影响因子：
64.8
作者：
Carmeliet, Peter;Jain, Rakesh K.
通讯作者：
Jain, Rakesh K.
影响因子：
48
作者：
Kamoun, Walid S.;Chae, Sung-Suk;Lacorre, Delphine A.;Tyrrell, James A.;Mitre, Mariela;Gillissen, Marijn A.;Fukumura, Dai;Jain, Rakesh K.;Munn, Lance L.
通讯作者：
Munn, Lance L.