Vascularization, the formation of new blood vessels, is an essential biological process. As the vasculature is involved in various fundamental physiological phenomena and closely related to several human diseases, it is imperative that substantial research is conducted on characterizing the vasculature and its related diseases. A significant evolution has been made to describe the vascularization process so that in vitro recapitulation of vascularization is possible. The current microfluidic systems allow elaborative research on the effects of various cues for vascularization, and furthermore, in vitro technologies have a great potential for being applied to the vascular disease models for studying pathological events and developing drug screening platforms. Here, we review methods of fabrication for microfluidic assays and inducing factors for vascularization. We also discuss applications using engineered vasculature such as in vitro vascular disease models, vasculature in organ-on-chips and drug screening platforms.
The assessment of rupture probability is crucial to identifying at risk intracranial aneurysms (IA) in patients harboring multiple aneurysms. We aimed to develop a computer-assisted detection system for small-sized aneurysm ruptures using a convolutional neural network (CNN) based on images of three-dimensional digital subtraction angiography. A retrospective data set, including 368 patients, was used as a training cohort for the CNN using the TensorFlow platform. Aneurysm images in six directions were obtained from each patient and the region-of-interest in each image was extracted. The resulting CNN was prospectively tested in 272 patients and the sensitivity, specificity, overall accuracy, and receiver operating characteristics (ROC) were compared to a human evaluator. Our system showed a sensitivity of 78.76% (95% CI: 72.30%–84.30%), a specificity of 72.15% (95% CI: 60.93%–81.65%), and an overall diagnostic accuracy of 76.84% (95% CI: 71.36%–81.72%) in aneurysm rupture predictions. The area under the ROC (AUROC) in the CNN was 0.755 (95% CI: 0.699%–0.805%), better than that obtained from a human evaluator (AUROC: 0.537; p < 0.001). The CNN-based prediction system was feasible to assess rupture risk in small-sized aneurysms with diagnostic accuracy superior to human evaluators. Additional studies based on a large data set are necessary to enhance diagnostic accuracy and to facilitate clinical application.
Fas ligand (FasL, CD178) is known to bind to its receptor (Fas, CD95) and mediate cellular apoptosis to maintain immune homeostasis. Recently, it has been recognized that tumor cells and their microenvironments allow an adjacent vascular endothelium to express the FasL on its cell membrane, utilizing the endothelium as an immune barrier to kill antitumor cytotoxic T cells. Here, a microfluidic tumor vasculature model is presented, which enables the recapitulation of an endothelial immune barrier expressing FasL. The in vitro three-dimensional model replicates enhanced endothelial FasL expression under the hypoxic tumor microenvironment. Apoptosis rates of FasL-susceptible target cells are augmented under the microenvironment with upregulated FasL but are consequently abrogated by administrations of pharmacological inhibitions, FasL–Fas blockades. The microfluidic system suggests its promising applications in elucidating complex immunosuppressive mechanisms of the tumor microenvironment and screening of cell-mediated immunotherapies as a preclinical model.
Hyperuricemia is a risk factor for cardiovascular disease and is associated with increased arterial stiffness in high-risk populations. However, given the possible sex-related differences in the prevalence of hyperuricemia, the association between elevated serum uric acid (SUA) level and increased arterial stiffness has yielded conflicting results. We investigated the relationship between SUA and arterial stiffness in asymptomatic healthy subjects who underwent a health examination. Subjects who underwent a comprehensive health examination were enrolled. After exclusion of extensive confounding factors, 2,704 healthy subjects with coronary calcium score < 100 were evaluated in the final analysis. All subjects underwent brachial—ankle pulse wave velocity (baPWV) to detect arterial stiffness. The SUA was divided into quartiles for its association with arterial stiffness and was analyzed separately for men and women. The mean SUA level was significantly lower in women than in men. The baPWV was significantly elevated in subjects with the highest quartile of SUA in women, but not in men. After adjusting for age, smoking, systolic blood pressure, body mass index, estimated glomerular filtration rate, fasting plasma glucose, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, and coronary artery calcium score, the highest quartile of SUA in women was significantly associated with increased risk of high baPWV compared with the lowest quartile of SUA (OR = 1.7, p = 0.018), whereas in men, SUA level was not associated with high baPWV. Our study showed that elevated SUA is independently associated with increased baPWV in healthy Korean women, but not in men.
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