Development of a 3D-3 co-culture microbead consisting of cancer-associated fibroblasts and human umbilical vein endothelial cells for the anti-tumor drug assessment of lung cancer.

Background: Drug resistance is a major challenge in the treatment of lung cancer. Increasing evidence indicates that the tumor microenvironment (TME), including cancer-associated fibroblasts (CAFs) and tumor endothelial cells (TECs), plays a significant role in determining the tumor sensitivity to therapeutic agents. There is, however, a dearth of models, two-dimensional (2D) or three-dimensional (3D), that represent the Methods: We established direct 3D micro-beads of primary lung cancer using conditional reprogramming (CR) technology and co-cultured them with CAFs and HUVECs to evaluate the effect of the TME compartment on tumor sensitivity to chemotherapeutic agents and tyrosine kinase inhibitors (TKIs). RNA sequencing (RNA-seq) was performed on the 3D micro-beads in tissue, mono-culture, and co-culture conditions to uncover transcriptional changes induced by tumor-stroma interaction. Results: The storage modulus of 3D hydrogel microbeads was shown to be 12 kPa, which is similar to that of lung tumor tissue and demonstrates good biocompatibility, making it suitable for constructing Conclusions: These findings suggest that the patient-derived