Low levels of physiological interstitial flow eliminate morphogen gradients and guide angiogenesis.
Low levels of physiological interstitial flow eliminate morphogen gradients and guide angiogenesis.
复制标题
DOI：
10.1007/s10456-017-9559-4
复制
发表时间：
2017-11
期刊：
影响因子：
9.8
通讯作者：
中科院分区：
文献类型：
--
作者：
对流输送会显著扭曲空间浓度梯度。间质流动在活组织中普遍存在，但我们对间质流动如何影响生物过程中的浓度梯度的理解有限。间质流动对血管生成特别有意义，因为病理和生理性血管生成与间质流动的改变有关，间质流动和形态梯度（如血管内皮生长因子，VEGF）都可能刺激和引导新血管的生长。我们设计了一个体外微流控平台来模拟三维血管生成的组织微环境，精确控制间隙流动和空间形态梯度。微血管组织是由从脐带血中提取的内皮集落形成细胞来源的内皮细胞（ECFC-ECs）和纤维蛋白细胞外基质中的间质成纤维细胞发育而成的。通过控制微流控管内的压力来控制间隙流动。建立了质量和动量传递的数学模型，并用荧光标记的葡聚糖进行了实验研究，以验证该平台。我们的数据表明，在生理间质流动（0.1至10µm/s）时，形态发生梯度在数小时内被消除，血管生成表现出与间质流动相反方向的显著偏向。间质血流定向血管生成依赖于VEGF的存在，其作用由αvβ3整合素介导。我们的结论是，在生理条件下，生长因子如VEGF和流体力共同作用，启动和空间引导血管生成。
Convective transport can significantly distort spatial concentration gradients. Interstitial flow is ubiquitous throughout living tissue, but our understanding of how interstitial flow affects concentration gradients in biological processes is limited. Interstitial flow is of particular interest for angiogenesis because pathological and physiological angiogenesis is associated with altered interstitial flow, and both interstitial flow and morphogen gradients (e.g., vascular endothelial growth factor, VEGF) can potentially stimulate and guide new blood vessel growth. We designed an in vitro microfluidic platform to simulate 3D angiogenesis in a tissue microenvironment that precisely controls interstitial flow and spatial morphogen gradients. The microvascular tissue was developed from endothelial colony forming cell-derived endothelial cells (ECFC-ECs) extracted from cord blood and stromal fibroblasts in a fibrin extracellular matrix. Pressure in the microfluidic lines was manipulated to control the interstitial flow. A mathematical model of mass and momentum transport, and experimental studies with fluorescently labeled dextran were performed to validate the platform. Our data demonstrate that at physiological interstitial flow (0.1 to 10 µm/s), morphogen gradients were eliminated within hours, and angiogenesis demonstrated a striking bias in the opposite direction of interstitial flow. The interstitial flow-directed angiogenesis was dependent on the presence of VEGF and the effect was mediated by αvβ3 integrin. We conclude that under physiological conditions, growth factors such as VEGF and fluid forces work together to initiate and spatially guide angiogenesis.
登录
查看更多内容
通过自导向的血管生成发芽的体外3D毛细管床的工程。
影响因子：
3.7
作者：
Chan JM;Zervantonakis IK;Rimchala T;Polacheck WJ;Whisler J;Kamm RD
通讯作者：
Kamm RD
影响因子：
6.1
作者：
Alonzo LF;Moya ML;Shirure VS;George SC
通讯作者：
George SC
影响因子：
10.3
作者：
Dreher, MR;Liu, WG;Chilkoti, A
通讯作者：
Chilkoti, A
影响因子：
56.9
作者：
BROOKS, PC;CLARK, RAF;CHERESH, DA
通讯作者：
CHERESH, DA
DOI：
10.1073/pnas.86.14.5385
发表时间：
1989-07-01
影响因子：
11.1
作者：
CHARY, SR;JAIN, RK
通讯作者：
JAIN, RK