Introduction: Hepatic stellate cell (HSC) activation is a key event in wound healing as well as in fibrosis development in the liver. Previously we developed a technique to induce HSC activation in slices from rat liver. Although this model provides a physiologic, multicellular milieu that is not present in current in vitro models it might still be of limited predictive value for the human situation due to species-differences. Therefore, we now aimed to evaluate the applicability of human liver slices for the study of HSC activation.
Method: Liver slices (8 mm diameter, 250 microm thickness) were generated from human liver tissue and incubated for 3 or 16 h with 0-15 microl of carbon tetrachloride (CCl4) after which ATP-content and expression levels of HSC (activation) markers was determined.
Results: Human liver slices remained viable during incubation as shown by constant ATP levels. Incubation with CCl(4) caused a dose-dependent decrease in viability and an increase in mRNA expression of the early HSC activation markers HSP47 and alphaB-crystallin, but not the late markers for HSC activation, alphaSMA and pro-collagen 1a1. Synaptophysin mRNA expression remained constant during incubation with or without CCl4, indicating a constant number of HSC in the liver slices.
Conclusion: We developed a technique to induce early toxicity-induced HSC activation in human liver slices. This in vitro model provides a multicellular, physiologic milieu to study mechanisms underlying toxicity-induced HSC activation in human liver tissue.