3D Printing for a Better Preclinical Cancer Model

Peritoneal cancer is a rare form of cancer that can be especially deadly as it frequently isn’t diagnosed until it’s in an advanced stage. Even as treatments for the cancer advance, there are still limits, such as poor tissue penetration with chemotherapy. In addition, current preclinical models haven’t managed to precisely reproduce the disease conditions. But researchers at Ghent University have developed a 3D bioprinted model that more accurately replicates peritoneal metastasis than any other models so far.

Preclinical models are important because they help scientists to test how well certain diseases will respond to certain drugs. If they’re unable to accurately reproduce the properties of the disease, however, they can’t get an accurate idea of how the actual illness will respond to treatment. One of the limitations of previous models is an inability to precisely replicate the dimensions and mechanical properties of the tumor, but the Ghent team was able to circumvent that obstacle by using 3D printing.

In a paper entitled “Heterocellular 3D scaffolds as biomimetic to recapitulate the tumor microenvironment of peritoneal metastases in vitro and in vivo,” which you can access here, the researchers describe how they 3D printed a scaffold from PLA and treated it with plasma and gelatin, allowing them to replicate the size, porosity, and mechanical and biochemical properties of metastasis conditions. They then cultivated a population of cancerous and interacting cells, creating a more clinically relevant model than had been achieved in previous studies.

A tumor isn’t just one type of cell – it’s made up of multiple cell populations that interact with each other, so a preclinical model needs to have those multiple types of cells as well. The Ghent researchers combined cancer-associated fibroblasts (CAF) with tumor cell lines. The combination of these cells resulted in the formation of tumor structures (spheroids) in vitro, which demonstrated the importance of CAF in preclinical models.

To test whether their models could reproduce metastasis conditions in vivo, the researchers implanted them in the peritoneal cavities of mice. After 11 weeks, they discovered that the implanted models presented a heterogeneous cell population, including the seeded CAF and proliferating cancer cells, as well as host cells such as immune, adipose and epithelial cells.

The constructs also promoted the formation of blood vessels, which the researchers believe is due to the interaction between the CAF and cancer cells. This produces signals that promote neovascularization. A comparison of the implanted constructs with a traditional metastasis model and a real tumor extracted from a patient showed that the immune response of the constructs was similar to that found in the actual tumor, unlike in the traditional model.

The 3D printed model is a big step forward from traditional models, and provides scientists with a better way to assess drug efficacy and penetrability, as well as a better tool for screening new therapies.

Authors of the study include Emiel De Jaeghere, Elly De Vlieghere, Jasper Van Hoorick, Sandra Van Vlieberghe, Glenn Wagemans, Leen Pieters, Elodie Melsens, Marleen Praet, Jo Van Dorpe, Matthieu N. Boone, Rouba Ghobeira, Nathalie De Geyter, Marc Bracke, Christian Vanhove, Sara Neyt, Geert Berx, Bruno G. De Geest, Peter Dubruel, Heidi Declercq, Wim Ceelen, and Olivier De Wever.

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[Source: MedicalPhysicsWeb/Images: Ghent University]