Effect of Heme Oxygenase Inducers and Inhibitors on the Anti fibrotic action of MSCs in Experimental Liver Fibrosis in Rats

Abstract

The purpose of this study was to evaluate the effect of MSCs or heme oxygenase inducer / inhibitor on liver fibrosis. Seventy female rats were involved in this study, sixty of which received carbon tetrachloride injection to induce liver fibrosis. Rats were divided into 7 groups: Control, Fibrotic group, Fibrotic group that received MSCs (MSCs were derived from the bone marrow of femoral and tibial bones of male rats. MSCs were separated, grown, and propagated in culture for 2 weeks. They were characterized morphologically, via detection of CD29 by RT-PCR, then they were stained with PKH-26), Fibrotic group that received HO inhibitor (zinc protoporphyrin), Fibrotic group that received HO inducer (cobalt protoporphyrin), Fibrotic group that received both HO inhibitor and MSCs and Fibrotic group that received both HO inducer and MSCs. HO gene expression (via Real Time- PCR) and activity were measured in the liver. Liver tissue was examined histopathologically and liver functions (ALT and serum albumin) were estimated for all groups. MSCs gave the best anti fibrotic effect, while heme oxygenase inducer / inhibitor didn’t produce a beneficial effect on liver fibrosis.