Xiaozhen Dai, Shaoxi Cai, Qunfang Ye, Jiahuan Jiang, Xiaoqing Yan, Xin Xiong, Qifeng Jiang, Albert Chih-Lueh Wang, Yi Tan
Chin Sci Bull. 2011 Nov 1;56(31):3301-3309. doi: 10.1007/s11434-011-4717-3.
Angiogenesis is very important for many physiological and pathological processes. However, the molecular mechanisms of angiogenesis are unclear. To elucidate the molecular mechanisms of angiogenesis and to develop treatments for "angiogenesis- dependent" diseases, it is essential to establish a suitable in vitro angiogenesis model. In this study, we created a novel in vitro angiogenesis model based on a microfluidic device. Our model provides an in vivo-like microenvironment for endothelial cells (ECs) cultures and monitors the response of ECs to changes in their microenvironment in real time. To evaluate the potential of this microfluidic device for researching angiogenesis, the effects of pro-angiogenic factors on ECs proliferation, migration and tube-like structure formation were investigated. Our results showed the proliferation rate of ECs in 3D matrix was significantly promoted by the pro-angiogenic factors (with an increase of 59.12%). With the stimulation of pro-angiogenic factors gradients, ECs directionally migrated into the Matrigel from low concentrations to high concentrations and consequently formed multi-cell chords and tube-like structures. These results suggest that the device can provide a suitable platform for elucidating the mechanisms of angiogenesis and for screening pro-angiogenic or anti-angiogenic drugs for "angiogenesis-dependent" diseases.
血管生成对许多生理和病理过程都非常重要。然而,血管生成的分子机制尚不清楚。为了阐明血管生成的分子机制并开发针对“血管生成依赖性”疾病的治疗方法,建立合适的体外血管生成模型至关重要。在本研究中,我们基于微流控装置创建了一种新型的体外血管生成模型。我们的模型为内皮细胞(ECs)培养提供了类似体内的微环境,并实时监测ECs对其微环境变化的反应。为了评估这种微流控装置在研究血管生成方面的潜力,研究了促血管生成因子对ECs增殖、迁移和管状结构形成的影响。我们的结果表明,促血管生成因子显著促进了三维基质中ECs的增殖率(增加了59.12%)。在促血管生成因子梯度的刺激下,ECs从低浓度向高浓度定向迁移到基质胶中,从而形成多细胞索和管状结构。这些结果表明,该装置可为阐明血管生成机制以及筛选针对“血管生成依赖性”疾病的促血管生成或抗血管生成药物提供合适的平台。