Bone marrow-derived mesenchymal stem cells: a potential therapy in an autoimmune hepatitis rat model

Background: Autoimmune hepatitis (AIH) is becoming more common worldwide. The therapy choices for AIH are still limited, with unfavorable side effects resulting in patients with a low quality of life. This study aims to study the therapeutic role of bone marrow-derived mesenchymal stem cells (MSCs) on AIH in the rat model. Methods: Twenty-nine white Wistar rats were used for a total of 53 days. Four groups were set up; Group I (5 rats) was used as the negative control (CON). Group II (24 rats) was administered Concanavalin A (Con A) 20 mg/kg ip once a week for five consecutive weeks. Sixteen rats from group II were divided among groups III and IV after stoppage of Con A and injected with 2 x106 BM-MSCs via tail vein. Group III (TTT-12) rats were sacrificed after 12 days and Group IV (TTT-18) after 18 days. Morphological, biochemical, histopathological, and immunohistochemical studies were conducted. Results: The administration of BM-MSCs lowered elevated serum levels of AST by 47% after 12 days and 19% after 18 days whereas the level of ALT decreased by 13% and 20.8%in group Con A. Serum inflammatory cytokines IL-10 and tumor necrosis factor alpha (TNF-alpha) increased in the Con A group were decreased in treated groups by 27% and 23% in TTT-12 and 22.8% and 1.8% in TTT-18. In group TTT-12, the area of Kupffer cells immunostained with CD68 was significantly reduced by 72%, whereas the BM-MSCs immunostained with CD44 were more intense by increasing by 257%. The therapeutic effect of BM-MSCs in group TTT-12 exceeded that in TTT-18 decreasing liver enzymes, inflammation and fibrosis, and restoring liver structure. Conclusions: BM-MSCs achieved a considerable short-term improvement in the AIH model; however, repeated injections were necessary to achieve a sustained therapeutic effect.