Article ID Journal Published Year Pages File Type
5855806 Regulatory Toxicology and Pharmacology 2016 11 Pages PDF
Abstract

•hUC-MSCs showed therapeutic effect in CCl4-induced acute liver injury model.•In 13-week toxicity study, NOAEL of hUC-MSCs was determined to be greater than 5 × 107/kg.•In 26-week tumorigenicity study, no mice developed hUC-MSC-related tumor up to 1 × 108/kg.•In biodistribution study, most of hUC-MSCs were cleared from major organs of mice at 13 weeks.

Umbilical cord-derived mesenchymal stem cells (UC-MSCs) therapy might be an alternative to liver transplantation for acute or chronic liver injury. The aim of this study was to evaluate the efficacy of human UC-MSCs on carbon tetrachloride (CCl4)-induced acute liver injury. In addition, its toxicity, tumorigenicity, and biodistribution were determined. Significant hepatoprotective effects of hUC-MSCs with decreased levels of hepatocellular necrosis and lobular neutrophilic infiltration were found. Regarding the safety of hUC-MSCs, no serious hUC-MSCs-related changes (body weight, food/water consumption, clinical symptom, urinalysis, hematology, clinical chemistry, organ weight, and histopathology) were observed in a 13-week subchronic toxicity study. In a 26-week tumorigenicity study, no mice developed tumor related to hUC-MSCs transplantation up to 1 × 108 cells/kg. In particular, human mitochondrial sequence detection revealed that most hUC-MSCs were cleared from the major organs of the mice at 13 weeks after transplantation. There was no systemic toxicity or neoplastic finding either. Taken together, these results suggested that hUC-MSCs have great potential for future clinical treatment of acute liver disease.

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