Presentation: 2025 ND EPSCoR Annual conference 

October 21, 2025, NDSU Memorial Union, Fargo, North Dakota

Effect of Extracellar Matrix Composition on Therapeutic Response of Pancreatic Ductal Adenocarcinoma Organoids

3D in vitro tumor models better mimic original tumor characteristics compared to 2D models. Matrigel®, an extracellular matrix (ECM) extracted from Engelbreth-Holm-Swarm mouse sarcoma cell culture, is the most commonly used commercial hydrogel product for developing and testing 3D in vitro pancreatic ductal adenocarcinoma (PDAC) models. However, the composition of Matrigel® is not reflective of the ECM content of PDAC. Additionally, PDAC tumors are often desmoplastic, consisting of up to 90% ECM by volume. This desmoplasia has been correlated with increased likelihood of metastasis, resistance to therapies, and patient mortality. To remedy this pitfall, we developed a novel hydrogel composed of ECM components which better reflect human PDAC tissue. We have demonstrated that 3D commercial and patient-derived cell lines grown in our hydrogel exhibit altered growth, metabolism, morphology, and response to chemotherapies compared to those grown in Matrigel®. Additionally, we show that expression of ECM fiber density and type varies widely between individual patients.These results provide preliminary evidence that the composition of the hydrogel used to generate 3D in vitro models may have an impact on their phenotypic properties. Further development and characterization of these models is expected to better reflect in vivo conditions and increase the predictive value of drug testing.