3D MicroOrganoSpheres Formation of Hepatocellular Carcinoma on Chip as a Novel in Vitro Model for Physiological and Therapeutic Studies

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third most frequent cause of cancer-related mortality worldwide. Recent advances in organoid technology have revolutionized the in vitro culture tools for biomedical research by creating powerful three-dimensional (3D) models to recapitulate the cellular heterogeneity, structure, and functions of organs and tissues. In this work, 3D MicroOrganoSpheres (MOSs) were developed from human liver cancer HepG2 cell lines (HCC-MOSs) embedded in methylcellulose and dispersed in mineral oil by a 2-channels droplet generator chip controlled by two separate pumps. The HCC-MOSs have been maintained in culture and their growth and development were monitored to create a preliminary model for organoids. MOSs on-chip can be used to simulate the complex structure, microenvironment, and biological functions of HCC and provide an in vitro model to study the physiological processes underlying the tumor and the response to therapeutic treatment.