Effect of Umbilical Cord Blood-Derived Stem Cells on Liver Tissue Regeneration in Canine Liver Injury Models

Abstract

The liver is a vital organ with an inherent regenerative capacity; however, in conditions of acute or chronic injury, this intrinsic ability may be insufficient, leading to hepatic dysfunction or failure. Recently, stem cell–based therapeutic strategies have gained growing attention as innovative approaches for the repair of damaged tissues. In the present study, we investigated the regenerative effects of canine umbilical cord blood–derived mesenchymal stem cells (cUCB-MSCs) on hepatic tissue recovery in experimentally induced liver injury models. Hepatic damage was established by controlled administration of carbon tetrachloride (CCl₄). The isolated cUCB-MSCs were purified, phenotypically characterized (CD90⁺, CD105⁺, CD34⁻, CD45⁻), and subsequently infused intravenously into the test animals. Evaluation parameters included serum biochemistry (ALT, AST, ALP, albumin, bilirubin), hepatic gene expression (albumin, HNF4α, CYP3A12), and histopathological analysis (H&E staining, fibrosis grading, nuclear size, and liver-to-body ratio). The results demonstrated that ALT and AST levels significantly declined (p < 0.05) in the treatment group, with a concurrent improvement in the albumin-to-bilirubin ratio. Gene expression analyses revealed approximately 2.5-fold and 2-fold increases in albumin and HNF4α expression, respectively, compared with the control group. Histologically, necrotic and inflammatory areas were notably reduced, and fibrosis severity decreased (mean fibrosis score: 1.8 vs. 3.2 in controls). These findings suggest that cUCB-MSCs possess a strong regenerative potential to restore hepatic architecture and function in canine liver injury models. Consequently, this stem cell–based therapy could serve as a promising adjunctive option for the treatment of severe liver damage in dogs. Further studies are warranted to optimize dosage, delivery routes, and evaluate long-term safety outcomes.