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

Jun Won Yun, Jae Hun Ahn, Euna Kwon, Seung Hyun Kim, Hanna Kim, Ja June Jang, Woo Ho Kim, Ji Hyang Kim, Su youne Han, Jin Tac Kim, Jong-Hoon Kim, Wookhwan Kim, Seung Yup Ku, Byung Rok Do, Byeong Cheol Kang

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12 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)437-447
Number of pages11
JournalRegulatory Toxicology and Pharmacology
Volume81
DOIs
Publication statusPublished - 2016 Nov 1

Keywords

  • Biodistribution
  • Liver injury
  • Toxicity
  • Tumorigenicity
  • Umbilical cord-derived mesenchymal stem cells

ASJC Scopus subject areas

  • Toxicology

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    Yun, J. W., Ahn, J. H., Kwon, E., Kim, S. H., Kim, H., Jang, J. J., Kim, W. H., Kim, J. H., Han, S. Y., Kim, J. T., Kim, J-H., Kim, W., Ku, S. Y., Do, B. R., & Kang, B. C. (2016). Human umbilical cord-derived mesenchymal stem cells in acute liver injury: Hepatoprotective efficacy, subchronic toxicity, tumorigenicity, and biodistribution. Regulatory Toxicology and Pharmacology, 81, 437-447. https://doi.org/10.1016/j.yrtph.2016.09.029