Objective: Hepatocellular carcinoma (HCC) is a major public health problem causing significant morbidity and mortality due to increasing prevalence and limited treatment options. Crosstalk between cancer cells and cells in the tumour microenvironment including cancer-associated fibroblast (CAFs) and macrophages aid cancer development, metastasis, and drug resistance to standard therapies such as Sorafenib. Effectively modelling these interactions in of primary importance to develop novel treatments. Researcher aimed to develop a new bio-printed HCC model that more accurately models the microenvironment and includes interactions between HCC cells and CAFs. 

Methods: Researcher used human SNU-449 HCC cells to model cancer cells, and LX-2 human myofibroblasts to model CAFs. he assessed responses to Sorafenib in two- and three-dimensional (3D) culture in the non-defined matrix BME2, and novel bio-printed 3D models using defined matrices developed by Inventia Life Sciences.

Results: Researcher established the effects of Sorafenib on SNU-449 and LX-2 cells viability in 2D model, therefore researcher compared Sorafenib effects between 2D and 3D (BME-2) models and established significance reduction on both SNU-449 and LX-2 cells viability. Then established Sorafenib effects in 3D BME-2 matrix & 3D bio-printed versus 2D using bio-printer on SNU-449 and established significance reduction of SNU-449 viability. Based on that researcher established effect of Sorafenib concentration on a multi-cellular model SNU-449 & LX-2 cells combined that mimic tumor stroma in 3D BME-2 matrix & 3D bio-printed versus 2D on inert and on plastic using bio-printer and significance reduction was observed on SNU-449 & LX-2 cells combined.

Significance: In this study, researcher successfully developed a new bio-printed HCC model by co-culturing SNU-449 cells (human HCC line) and LX-2 cells (human HSC line) and tested the effect of increase concentration Sorafenib in 2D Vs 3D using RASTRUM bio-printer.

Keywords: Hepatocellular Carcinoma, Cell Interaction, Hepatic Stellate Cell, Cancer Cells, Organoids, Tumor Microenvironment, Drug Resistance