Intravenous Umbilical Cord-derived Mesenchymal Stem Cells Transplantation Regulates Hyaluronic Acid and Interleukin-10 Secretion Producing Low-grade Liver Fibrosis in Experimental Rat.

Abstract

Introduction:Immunomodulation properties of mesenchymal stem cells have attracted tremendous attention that eventually could regress liver fibrosis process.Aim:The study aims to demonstrate the immunomodulation activities of Umbilical cord-derived Mesenchymal stem cells (UC-MSCs) affecting interleukin-10 (IL-10) and hyaluronic acid (HA) secretion post intraperitoneal injection of CCl4, potent hepatotoxin, induced liver fibrosis among experimental rats.Methods:There were 18 Sprague-Dawley (SD) rats divided into three treatment groups (G1 sham group, G2 untreated liver fibrosis group, and G3 UC-MSCs treated-group) and isolated in Stem Cell and Cancer Research Facility, Semarang, Indonesia. Blood examination was conducted after 3 and 14 days of UC-MSCs transplantation using sandwich based ELISA followed by the histopathological analysis of rat liver tissue. ANOVA and posthoc LSD tests were determined the significance against all groups based on their quantitative measurement.Results:UC-MSCs have been successfully extracted and isolated as well as positive with osteogenic differentiation (Alizarin dye). In further analysis, there were significant mean differences among all groups through the ANOVA test, both IL-10 and HA secretion, concurrent with low-grade liver fibrosis in G3. IL-10 elevates during the early phase of UC-MSCs transplantation, and HA significantly reduced on the 14th day of transplantation, it characterizes the liver fibrosis that has been attenuated.Conclusion:The transplantation of UC-MSCs has given an opportunity for the treatment of a wide range of chronic liver diseases through the immunomodulation properties via its paracrine effects that regulate specific cytokine to suppress fibrosis development.