Nondestructive Optical Toxicity Assays of 3D Liver Spheroids with Optical Coherence Tomography

Drug-induced liver injury (DILI) is the leading cause of failure in preclinical drug development and withdrawals. Given the central role of the liver in drug metabolism and detoxification, strong incentives exist to create new physiologically relevant, human-based, 3D in vitro liver models which will offer better prediction of DILI. However, most cell metabolic assays are designed for 2D culture and are not always suitable to assess 3D cultures; in addition, there is an emerging need to develop novel nondestructive assays to assess cell activity in a time-lapse fashion. In this study, optical coherence tomography (OCT) is used to measure the viability on 3D liver spheroids after acetaminophen exposure used as a model of DILI. Using HepaRG cells, 3D liver spheroids are grown simultaneously to the conventional 2D DILI model for 9 d and are exposed to 5, 10, 20, and 40 x 10(-3) M acetaminophen for 24 h. It is shown that OCT can image noninvasively, and label free, the cell metabolic activity, thus enabling the assessment of viability of the 3D spheroids. This correlates well with cellular metabolic activity measured by biochemical assays. This method is translatable to any 3D tissue model and can be performed using any commercial OCT system.