Background : Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality globally. Understanding the mechanisms of liver disease progression, including HCC, is vital. Hepatic organoids, which mimic liver tissue ex vivo, provide a novel platform for these studies.

Methods : This study advances organoid research by employing a non-physical co-culture system, integrating fibroblasts isolated from normal human liver tissue with tumor-derived organoids. Our objective was to enhance the growth rate and purity of cancer organoids without direct physical interaction between organoids and fibroblasts.

Results : The non-physical co-culture system significantly increased the surface area of both normal and tumor-derived organoids within ten days. This method effectively reduced fibroblast contamination, allowing for the exclusive cultivation of liver tumor-derived organoids. ELISA analysis showed an increase in cytokine A levels in the culture medium, indicative of its role in promoting tumor organoid growth. Furthermore, tumor organoids from this co-culture system demonstrated accelerated growth in balb/c nude mice compared to tumor organoids cultured alone.

Conclusions : Our findings suggest that the non-physical co-culture system stimulates cytokine A secretion from normal liver fibroblasts, enhancing tumor organoid growth. This highlights the potential role of cytokine A in tumor development and offers insights for new therapeutic approaches. Additionally, our method optimizes the production of patient-specific organoids, presenting a promising avenue for personalized treatment and drug screening platforms.