Human mesenchymal stem cell secretome lowers caspase-3 levels and apoptosis in hepatocytes of cholestatic rats

Abstract

Liver cirrhosis is ranked 15th as a cause of morbidity and is ranked 11th as a leading cause of mortality in the world. Definitive therapy is liver transplantation, but it is constrained by difficulties in finding a transplant donor Hu MSCs cell-based therapy can help liver regeneration directly, through hepatogenic differentiation, or indirectly through the paracrine secretome. This study aims to determine the effect of Human Mesenchymal Stem Cell Secretome administration on caspase 3 levels and apoptotic hepatic cell count in a rat model with cholestasis after choledochal duct ligation receiving standard UDCA (Urso Deoxy Cholid Acid) therapy. Twenty-four male Wistar rats were subjected to a choledochal duct ligation and were included in this randomized experimental study. After surgical intervention, all rats were randomly assigned into 4 group; control, administration of UDCA, Hu MSC-S, and a combination of UDCA and Human Mesenchymal Stem Cell Secretome for 4 weeks. Caspase-3 levels were assessed from the blood sample, while the apoptosis of hepatocyte evaluated using histopathologic examination of the liver. Caspase-3 levels was significantly lower in the UDCA and Human Mesenchymal Stem Cell Secretome treated groups (6.23 ± 0,30), compared to the UDCA (8.77 ± 0.55) and Human Mesenchymal Stem Cell Secretome alone (7.30 ± 0.42) (ANOVA p < 0,05). The apoptosis of hepatocyte was significantly lower in the combination group (8,88 ± 5,46) compared to the UDCA (29,00 ± 4,52) and Human Mesenchymal Stem Cell Secretome alone (20,83 ± 4,14) (ANOVA p < 0,05). In conclusion, addition of Human Mesenchymal Stem Cell Secretome to UDCA lowered caspase-3 levels and apoptotic cell count in rats with hepatic cholestasis after choledochal duct ligation and better compared to each alone. Keywords: Mesenchymal Stem Cell Secretome, Capsase-3, Apoptotic Cell, Liver Regeneration, Cholestasis