Abstract
Primary human tissue cultures provide a more ethically sound and potentially effective\r alternative model to animal testing. It has been shown that culture of two or more cells\r together provides improved epithelial polarization and differentiation in culture in vitro.\r Two non-parenchymal (NPC) liver cell types, Kupffer cells (KCs) and Liver Sinusoidal\r Endothelial Cells (LSECs), are located in close proximity in the liver sinusoid. As drug\r metabolism is a species- specific process, it is important to re-evaluate rat hepatic coculture\r experiments with human hepatocytes and NPCs. In order to accurately\r recapitulate liver responses in vitro, NPC such as KC must be incorporated into existing\r liver culture models. In an effort to incorporate KC into the Liver-On-A-Chip, I examined\r the relationship between human KCs and LSECs, and between hepatocytes and LSECs.\r In addition to morphological study, I examined the viability and functionality of\r hepatocyte microfluidic co- and monocultures by looking at lactose dehydrogenase\r (LDH) release, albumin secretion, and metabolic CYP3A4 activity. Hepatocyte-LSEC\r microfluidic co-culture revealed decreased LDH release after the first few days of flow\r compared to hepatocyte static monoculture controls. Moreover, Liver-On-A-Chip\r cultures displayed comparable albumin synthesis when compared to in vivo data. KCLSEC\r co-culture maintained morphology and viability better than KC monoculture\r alone. Examination of KC-LSEC compatibility in static culture shows that further\r optimization is required to incorporate KC into liver tissue culture models in an\r organized manner.