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

Abstract

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-α) 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.Keywords: Liver; Autoimmunity; MSCs; Inflammatory cytokines; CD68; CD44; Histopathology  Editorial Expression of Concern:20 May 2025: Following publication of this paper, the internal audit (consequent to concerns on quality raised by Web of Science) notified Advancements in Life Sciences about quality of figures. By this Editorial Expression of Concern, we alert the scientific community of the errors as we refurnish figures with higher DPI.Editorial Note:28 May 2025:  Readers may please see figures with higher DPI given at the end of Results section in the HTML version. Expression of concern is hereby revoked