Xu Yingqian, Deng Jia, Hao Shilei, Wang Bochu
Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, China.
Chongqing Engineering Research Center of Pharmaceutical Sciences, Chongqing Medical and Pharmaceutical College, Chongqing 401331, China.
Life (Basel). 2022 Mar 15;12(3):427. doi: 10.3390/life12030427.
Current in vitro vascular models are too simple compared with the real vascular environment. In this research, a novel in vitro 3D vascular disease model that simulated the vascular microenvironment was introduced.
This model was mainly established by low shear stress and co-culture of endothelial cells and smooth muscle cells. Characterization and reproduction of the pathological state of the 3D model were determined. The effect of two clinical drugs was verified in this model. The difference of drug screening between a traditional oxidative-damaged cell model and this 3D model was determined by HPLC.
This model presented many disease markers of vascular diseases: abnormal cellular shape, higher endothelial cell apoptotic rate and smooth muscle cell migration rate, decreased superoxide dismutase level, and increased malondialdehyde and platelet-derived growth factor level. The drugs effectively reduced the disease indices and relieved the damage caused by low shear stress. Compared to the traditional oxidative-damaged cell model, this 3D model screened different active components of extract, and it is closer to clinical studies.
These results suggest that the 3D vascular disease model is a more efficient and selective in vitro study and drug screening platform for vascular diseases than previously reported in vitro vascular disease models.
与真实的血管环境相比，当前的体外血管模型过于简单。在本研究中，引入了一种模拟血管微环境的新型体外三维血管疾病模型。
该模型主要通过低剪切应力以及内皮细胞与平滑肌细胞的共培养建立。确定了三维模型病理状态的表征和重现性。在该模型中验证了两种临床药物的效果。通过高效液相色谱法确定传统氧化损伤细胞模型与该三维模型在药物筛选方面的差异。
该模型呈现出许多血管疾病的疾病标志物：细胞形态异常、内皮细胞凋亡率和平滑肌细胞迁移率升高、超氧化物歧化酶水平降低以及丙二醛和血小板衍生生长因子水平升高。药物有效降低了疾病指标并减轻了低剪切应力造成的损伤。与传统氧化损伤细胞模型相比，该三维模型筛选出了提取物的不同活性成分，且更接近临床研究。
这些结果表明，与先前报道的体外血管疾病模型相比，三维血管疾病模型是一种更高效、更具选择性的用于血管疾病的体外研究和药物筛选平台。
