The role of cyclic AMP in normalizing the function of engineered human blood microvessels in microfluidic collagen gels.
The role of cyclic AMP in normalizing the function of engineered human blood microvessels in microfluidic collagen gels.
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DOI：
10.1016/j.biomaterials.2010.02.041
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发表时间：
2010-06
期刊：
影响因子：
14
通讯作者：
Tien, Joe
中科院分区：
文献类型：
--
作者：
Wong, Keith H. K.;Truslow, James G.;Tien, Joe
几乎所有的工程组织最终都必须血管化才能存活。为此，我们和其他人最近开发了合成含有开放微流体网络的细胞外基质支架的方法。这些支架作为形成可灌注的内皮管的模板；这些微血管结构是否稳定和/或有功能在很大程度上是未知的。在这里，我们发现提高细胞内第二信使环AMP （cAMP）浓度的化合物强烈地正常化了微流控I型胶原凝胶中工程化人微血管的表型。环状amp升高剂促进血管稳定性和屏障功能，减少细胞周转。在诱导最高水平cAMP的条件下，体外工程微血管的生理状况在数量上反映了体内天然血管的生理状况。计算分析表明，cAMP稳定血管的部分原因是其增强屏障功能。
Nearly all engineered tissues must eventually be vascularized to survive. To this end, we and others have recently developed methods to synthesize extracellular matrix-based scaffolds that contain open microfluidic networks. These scaffolds serve as templates for the formation of endothelial tubes that can be perfused; whether such microvascular structures are stable and/or functional is largely unknown. Here, we show that compounds that elevate intracellular concentrations of the second messenger cyclic AMP (cAMP) strongly normalize the phenotype of engineered human microvessels in microfluidic type I collagen gels. Cyclic AMP-elevating agents promoted vascular stability and barrier function, and reduced cellular turnover. Under conditions that induced the highest levels of cAMP, the physiology of engineered microvessels in vitro quantitatively mirrored that of native vessels in vivo. Computational analysis indicated that cAMP stabilized vessels partly via its enhancement of barrier function.
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