Regul Toxicol Pharmacol. 2016 Sep 28. pii: S0273-2300(16)30277-X. doi: 10.1016/j.yrtph.2016.09.029. [Epub ahead of print]

Human umbilical cord-derived mesenchymal stem cells in acute liver injury: Hepatoprotective efficacy, subchronic toxicity, tumorigenicity, and biodistribution.

Yun JW¹, Ahn JH², Kwon E¹, Kim SH¹, Kim H¹, Jang JJ³, Kim WH³, Kim JH⁴, Han SY⁴, Kim JT⁴, Kim JH⁵, Kim W⁶, Ku SY⁷, Do BR⁸, Kang BC⁹.

Abstract

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.