基于嵌套阵列芯片的胃癌类器官模型构建及其在药敏检测中的应用研究OA

AIM:To construct a patient-derived gastric cancer organoid(PDO)model using a nested array chip and evaluate its utility in personalized drug screening.METHODS:Tissue specimens were obtained from eight gas-tric cancer patients during surgical resection.The specimens were digested,dissociated,and then mixed with 50%Matri-gel.An 8 µL aliquot of the mixture was seeded into the 3D implantation holes of the chip.Hematoxylin and eosin(HE)staining,along with immunohistochemical staining,were employed to validate the histomorphological and immunological marker consistency between the PDOs and the primary tumor tissues.Drug sensitivity screening was conducted using monotherapies of Paclitaxel,5-fluorouracil(5-FU),and oxaliplatin,as well as the 5-FU+oxaliplatin(FOLFOX)combina-tion regimen.The viability of the chip-based PDO model for drug screening was evaluated by integrating imaging analyses.RESULTS:Six PDO lines were successfully cultured,encompassing 2 intestinal-type,2 diffuse-type,and 2 mixed-type organoids.The PDOs displayed individual variations in morphology and growth characteristics.Notably,they exhibited identical morphological features and comparable immunological marker expression patterns to their corresponding primary tumors.More significantly,the drug response outcomes obtained from the chip-based model mirrored the heterogeneous re-sponses among individual patients,with the differential drug sensitivity profiles aligning well with the actual clinical re-sponses.CONCLUSION:The preliminary verification established the feasibility of utilizing PDOs on this nested array chip as an in vitro platform for drug screening.