Effect of Mechanical Stress Imposition on Co-culture of Hepatic Parenchymal and Nonparenchymal Cells: Possibility of Stimulating Production of Regenerating Factor

Abstract

The effect of mechanical stress generated within a three-dimensional bioreactor on the co-culture of hepatic parenchymal cells (PC) and hepatic nonparenchymal cells (NPC) was assessed to develop a bioartificial liver that can produce factors accelerating liver regeneration. A rotating radial flow bioreactor was used to provide mechanical stress to a co-culture of PC and NPC that were isolated from rats. They were co-cultured in the reactor under static or dynamic conditions. Albumin, interleukin-6 (IL-6), hepatocyte growth factor (HGF), and lactate dehydrogenase (LDH) were measured at intervals. Electron microscopy was also performed. LDH was not significantly different between the static and mechanical stress-loaded cultures, while albumin and interleukin-6 levels were higher in the latter at all sampling times. Only the co-cultures loaded with mechanical stress produced HGF in the early stage of culture (hours 3 and 6). Histologically, the cells retained their structure when cultured under dynamic conditions. These results suggested that an appropriate level of mechanical stress enabled co-cultures of PC and NPC to produce IL-6, HGF, and other factors that accelerate liver regeneration.