Abstract 159: Vascularized 3D cancer organoid research platform using surface acoustic waves
Authors: Kim Hyoyoung , Lee Yunam , Kang Byungjun , Yun Un-Jung , Choi Yunjung , Kim So Hui , Kim Hyunki , Lee Hyungsuk , Jung Minkyu 
Published: June 2023

Recently, organoids have been widely used in cancer research. However, cancer organoids have limitation in reflecting physicochemical microenvironments of tumor. In particular, vascular networks not only provide oxygen and nutrients to the tumor, but also play an important role as a channel through which drugs move in cancer. Vascularization occurs in an uncontrollable form and speed in conventional methods. Here, we regulate the directionality of the vascular bed using the surface acoustic waves(SAW) technology by which, vascular cells are locally aligned. Aligned cells exhibited an improved, cell-cell contact enhancing the vascular system maturation in a couple days. Organoids are constructed from gastric cancer patients with four molecular subtypes according to TCGA. Organoids were dissociated into a single cell to make a co-culture spheroid with HUVEC cells. Co-cultured spheroids were formed by adding fibronectin according to the characteristics of the patient sample. The SAW device is built with interdigitated transducer, NiNbO3 substrate, polydimethylsiloxane(PDMS) and coverglass. After putting co-culture spheroids and HUVEC cells mixed with fibrin gel into the device, patterning is performed using surface acoustic waves with shaking in EGM-2 media. After fixing the models, CD31 and F-actin are stained and imaged through immunofluorescent. Immunohistochemistry was performed to confirm the blood vessel cross section. The blood vessels patterned with SAW were well aligned in a straight line, and a lumen structure was formed in a couple days. When co-cultured spheroids were used compared to mono-cultured spheroids, the interaction with external HUVECs was improved, allowing for efficient vascular organism models. As evidence for this, it was confirmed that HUVEC inside the co-cultured spheroid and HUVEC outside were connected through interaction when PKH dyeing was done in a different color. We showed that blood vessels are formed faster and thicker in patterning models than in random models, and interactions with co-cultured spheroids are also high. Through immunofluorescent staining, we found that the number of vascular branches linked to spheroids was higher in the SAW model. In addition, in the H&E results, it was confirmed that the blood vessels were arranged in a line, and that differentiation occurred appropriately to form a tubular structure. In addition, the number of blood formed inside the spheroid was higher. Currently, this model is used to test anti-cancer efficacy using FGFR inhibitors and ramucirumab in FGFR2-amplified patient-derived organoids. An efficient vascularized 3D cancer organoid model was constructed using acoustic waves. Our vascularized 3D cancer organoid research platform will be applied for specific drug screening platform that directly aid the treatment of the specific patients with various drugs including chemoagents, targeted drugs, and immune checkpoints inhibitors.

Citation Format: Hyoyoung Kim, Yunam Lee, Byungjun Kang, Un-Jung Yun, Yunjung Choi, So Hui Kim, Hyunki Kim, Hyungsuk Lee, Minkyu Jung. Vascularized 3D cancer organoid research platform using surface acoustic waves [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 159.