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Cancer Technologies

Engineered Cancer Models for In Vitro Studies

Novel Vascularized Liver Tumor Model For Evaluation Of Vessel Regression And Cell Death Response To Embolic Agents

Saturday, October 26, 2024
8:45 AM – 9:00 AM EST
Location: Room 337

Introduction: Chemoembolization is a widely recognized treatment modality for liver cancer. Traditional testing of embolic agents often relies on animal models, which do not accurately replicate human vascular anatomy, presenting challenges in real-time vascular response evaluation. Our study introduces a novel in vitro microfluidic device featuring a vascularized human liver tumor model, designed to improve the testing of embolic agents and the assessment of chemotherapy release, bridging the gap between conventional animal models and human clinical settings.

Materials and

Methods: In our approach, a vascular bed was constructed by seeding a fibrin suspension with endothelial cells and fibroblasts. This arrangement enabled the formation of perfusable vascular networks within 5 days. Liver tumor spheroids were embedded centrally in a mix of collagen and fibrin within this setup (Figure 1A). We employed a novel drug-eluting shear thinning material (DESTH), injected via a 5Fr catheter into the microfluidic device, to simulate the chemoembolization process (Figure 1B). Control flow experiments included the use of drug-free shear-thinning materials and commercially available Embozene™ microspheres for comparison.

Results, Conclusions, and Discussions: Results and

Discussion: The functionality of the vascular bed was confirmed by the perfusion of a dextran dye, which demonstrated rapid distribution across the microchannels before the application of DESTH (Figure 1B i and v). After DOX-loaded DESTH was injected, dextran could not diffuse into the vascular bed (Figure 1B-ii). Fluorescence microscopy revealed significant vascular bed collapse within 24 to 48 hours post-treatment (Figure 1B iii and iv). Comparative analysis using live/dead staining showed high viability in control samples, whereas significantly increased cell death was observed in tumor spheroids treated with DOX-loaded DESTH (Figure 1C). Additionally, a flow experiment study with a control device is used to show the embolization efficiency of our shear thinning hydrogel (Figure 1D). Comparison of STH with commercial beads (EmbozeneTM Microspheres) using colored dyes showing flow can cross fibrin gel faster in control devices than embolized devices (Figure 1E). Microvasculature regression is then observed in devices treated with STB25 but not control device (Figure 1Fi, ii). In device treated with Embozene Microspheres, microvasculatures regress partially, mainly in the area closed to the embolized channel (Fig.1Fiii).

Conclusions: The developed microfluidic device with a vascularized liver tumor model has demonstrated significant potential in evaluating the effectiveness of different embolic agents. The study underlines the utility of this model over traditional animal-based models by enabling direct observation and assessment of embolic and chemotherapeutic interventions in a human-like tumor microenvironment. This platform could pave the way for more precise and tailored therapeutic strategies, potentially reducing the need for animal testing and accelerating the translation of embolic agents into clinical practice.

Acknowledgements (Optional): This work was supported by the National Institutes of Health (R01AR074234, R01AR073135, UH3TR003148, R34NS126032, R01 CA257558-01A1 and R01GM126571).