Intravenous Injection of Umbilical Cord-Derived Mesenchymal Stem Cells Improved Regeneration of Rat Liver after 2AAF/CCl₄-Induced Injury

Abstract

The effectivity of Mesenchymal Stem Cell (MSC) therapy for chronic liver injury is still questioned due to its possibility to have a pro-fibrotic effects. Other consideration is the preferably peripheral Intravenous (IV) route of application rather than direct to the target organ, such as portal vein or splenic vein, since the most of MSC will be trapped in the lung and other organs. Therefore, a study has been carried out in an animal model of chronic liver injury, 2AAF/CCl₄ rats, to find out whether IV injection of single dose, 1×10⁶ human umbilical cord-derived MSC (hUC-MSC) can regenerate the liver tissue and reduce the fibrosis. Male Wistar rats (n = 18, 8 weeks, 160-200 g) were divided into three groups of six rats, i.e., group I (control/healthy rats), group II (2AAF/CCl₄-induced liver injury with hUC-MSCs injected rats) and group III (2AAF/CCl₄-incuded liver injury without hUC-MSCs injected rats). Gross anatomical features of the livers and blood examination were tested. There was no significant different of the alanine Aminotransferase (ALT) and albumin serum level between groups; however there was a tendency of ALT decrease and Albumin increase in stem cells treated rats (group II). Histopathological observation using hematoxylin eosin and Masson’s trichrome staining showed an improvement in the liver damage condition (reduction of necrosis and coverage area of fat degeneration) and an improvement in the fibrosis condition in the group II compared to the group III. None of group II rat had fallen into cirrhosis as seen in group III. Immunohistochemistry staining against caspase 3 (biomarker for apoptosis) also showed significant reduction (p = 0.038; Tukey multiple comparison test) of group II expression index (2.74%) compared to the group III (8.64%). In conclusion, IV injection of single dose, 1×10⁶ hUC-MSC could regenerate the liver tissue and reduce the fibrosis in 2AAF/CCl₄ rats model of chronic liver injury.