Preclinical efficacy assessment of umbilical cord mesenchymal stem cell therapy for acute liver failure.

Objectives: Acute liver failure (ALF) is a life-threatening condition marked by rapid hepatocellular damage. This study investigates the therapeutic efficacy of human umbilical cord-derived mesenchymal stem cells (hUCMSCs) in a rat model of ALF. Materials and Methods: ALF was induced using D-galactosamine and lipopolysaccharide in rats. hUCMSCs were administered intravenously at different time points and dosages. Liver function, inflammatory cytokine levels, histopathology, neutrophil infiltration, and survival rates were evaluated. Additionally, biodistribution was tracked using 89Zr-labeled hUCMSCs, and fresh versus cryopreserved cells were compared. Results: Administration of hUCMSCs, especially at the prog-2h time point, significantly improved survival and liver histology. Treatment reduced ALT and AST levels and modulated pro- and anti-inflammatory cytokines. Neutrophil infiltration was alleviated by both fresh and cryo-preserved hUCMSCs. Biodistribution data revealed hepatic enrichment of hUCMSCs peaking at 24 hr post-injection. Conclusion: hUCMSCs exhibit strong immunomodulatory and hepatoprotective properties in ALF, offering promise for clinical translation. Timing and dosage significantly influence therapeutic efficacy, and cryopreserved cells maintain functionality comparable to that of fresh cells.