3D tumor angiogenesis models: recent advances and challenges

The development of blood vessels, referred to as angiogenesis, is an intricate process regulated spatially and temporally through a delicate balance between the qualitative and quantitative expression of pro and anti-angiogenic molecules. As angiogenesis is a prerequisite for solid tumors to grow and metastasize, a variety of tumor angiogenesis models have been formulated to better understand the underlying mechanisms and associated clinical applications. Studies have demonstrated independent mechanisms inducing angiogenesis in tumors such as (a) HIF-1/VEGF mediated paracrine interactions between a cancer cell and endothelial cells, (b) recruitment of progenitor endothelial cells, and (c) vasculogenic mimicry. Moreover, single-cell sequencing technologies have indicated endothelial cell heterogeneity among organ systems including tumor tissues. However, existing angiogenesis models often rely upon normal endothelial cells which significantly differ from tumor endothelial cells exhibiting distinct (epi)genetic and metabolic signatures. Besides, the existence of intra-individual variations necessitates the development of improved tumor vascular model systems for personalized medicine. In the present review, we summarize recent advancements of 3D tumor vascular model systems which include (a) tissue engineering-based tumor models; (b) vascular organoid models, and (c) organ-on-chips and their importance in replicating the tumor angiogenesis along with the associated challenges to design improved models.

Evaluation of the differences in pressure applied to the vessel wall by different types of balloon remodeling microcatheters in an experimental model

Background We examined compliance differences among balloon remodeling microcatheters, which have not been established previously. Methods Straight and 120° angulated vascular models were created in a 3 mm diameter tube with 3 mm hole (vascular model A), a tube with a 4 mm hole (vascular model B), and a 4 mm diameter tube (vascular model C). We compared the pressure exerted when each balloon was herniated 1 or 2 mm between three compliant balloons (SHOURYU SR, TransForm C, and Scepter C) and four super-compliant balloons (HyperForm, SHOURYU HR, TransForm SC, and Scepter XC). Results In vascular model A, there was a significant difference in the pressure exerted by compliant balloons and super-compliant balloons in both the straight and angulated models. In the straight model (1 and 2 mm), the lowest pressure was exerted by HyperForm (super-compliant balloons group) and SHOURYU SR (compliant balloons group). The lowest pressure was exerted in the angulated model by HyperForm (super-compliant balloons group) and Scepter C (compliant balloons group). The Scepter balloon exerted higher pressure in the straight model than other balloon remodeling microcatheters but less in the angulated model. In vascular model B, the pressure decreased in all balloons compared with model A. In vascular model C, the pressure increased in all balloons compared with model A. Conclusions Pressure differed across balloon remodeling microcatheters. In addition, vessel shape and diameter, and hole size, affected the results. Our findings can help select balloon remodeling microcatheters.

Accuracy of registration techniques and vascular imaging modalities in fusion imaging for aortic endovascular interventions: a phantom study

Background This study aimed to assess the error of different registration techniques and imaging modalities for fusion imaging of the aorta in a standardized setting using a anthropomorphic body phantom. Materials and methods A phantom with the 3D printed vasculature of a patient suffering from an infrarenal aortic aneurysm was constructed. Pulsatile flow was generated via an external pump. CTA/MRA of the phantom was performed, and a virtual 3D vascular model was computed. Subsequently, fusion imaging was performed employing 3D-3D and 2D-3D registration techniques. Accuracy of the registration was evaluated from 7 right/left anterior oblique c-arm angulations using the agreement of centerlines and landmarks between the phantom vessels and the virtual 3D virtual vascular model. Differences between imaging modalities were assessed in a head-to-head comparison based on centerline deviation. Statistics included the comparison of means ± standard deviations, student’s t-test, Bland-Altman analysis, and intraclass correlation coefficient for intra- and inter-reader analysis. Results 3D-3D registration was superior to 2D-3D registration, with the highest mean centerline deviation being 1.67 ± 0.24 mm compared to 4.47 ± 0.92 mm. The highest absolute deviation was 3.25 mm for 3D-3D and 6.25 mm for 2D-3D registration. Differences for all angulations between registration techniques reached statistical significance. A decrease in registration accuracy was observed for c-arm angulations beyond 30° right anterior oblique/left anterior oblique. All landmarks (100%) were correctly positioned using 3D-3D registration compared to 81% using 2D-3D registration. Differences in accuracy between CT and MRI were acceptably small. Intra- and inter-reader reliability was excellent. Conclusion In the realm of registration techniques, the 3D-3D method proved more accurate than did the 2D-3D method. Based on our data, the use of 2D-3D registration for interventions with high registration quality requirements (e.g., fenestrated aortic repair procedures) cannot be fully recommended. Regarding imaging modalities, CTA and MRA can be used equivalently.

BEHAVIORAL REACTIONS AND COGNITIVE FUNCTIONS IN RATS WITH VASCULAR MODEL OF ALZHEIMER'S TYPE DEMENTIA AT THE DIFFERENT STAGES OF DISEASE BEFORE AND AFTER STEM CELL CORRECTION

Background. The last researches offer to conduct the study of Alzheimer disease (AD) mechanisms using diverse experimental models. However, it was not investigated the behavioral and cognitive impairment in rats at the different stages of vascular model of dementia of Alzheimer’s type developed by us. Subjects and methods. The experiment was performed on 32 male WAG rats weighing 180-250 g which were divided into 4 groups. Rats from group 1 and 3 were injected by aqueous solution of sodium nitrite at a dose of 50 mg/kg of body mass intraperitoneally during 14 and 28 days respectively. Groups 2 and 4 were received 500,000 mesenchymal stem cells in suspension intravenously against the background of experimental nitrite-induced AD. To estimate the behavioral reactions and cognitive functions the Open Field Test (OFT) and Passive Avoidance test (PAT) were used. Results. In all experimental groups in most cases it was found the significant decrease in vertical and horizontal activity (p <0,05) and an increase in the number of defecation in the OFT. Rats from group 3 had the drop in locomotor, research and orientation activity. In the OFT and PAT in groups 2,4 it was observed an improvement in research activity and significant cognitive functions recovery (p=0,012) after stem cell correction. Conclusions. It was found the progression of the protective inhibition and cognitive impairment during experiment. The stem cells introduction had positive effects on brain function recovery.