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Regul Toxicol Pharmacol. 2016 Nov;81:437-447. doi: 10.1016/j.yrtph.2016.09.029. Epub 2016 Sep 28.

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

Author information

1
Department of Experimental Animal Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
2
Graduate School of Translational Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
3
Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea.
4
Biotechnology Research Institute, Hurim BioCell Co. Ltd., Seoul, Republic of Korea.
5
Laboratory of Stem Cell Biology, Division of Biotechnology, Department of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
6
Department of General Surgery, Ajou University School of Medicine, Suwon, Republic of Korea.
7
Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Republic of Korea.
8
Biotechnology Research Institute, Hurim BioCell Co. Ltd., Seoul, Republic of Korea. Electronic address: brokdo@nuri.net.
9
Department of Experimental Animal Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea; Graduate School of Translational Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea; Biomedical Center for Animal Resource and Development, Seoul National University College of Medicine, Seoul, Republic of Korea; Designed Animal and Transplantation Research Institute, Institute of GreenBio Science Technology, Seoul National University, Pyeongchang-gun, Gangwon-do, Republic of Korea. Electronic address: bckang@snu.ac.kr.

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.

KEYWORDS:

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

PMID:
27693706
DOI:
10.1016/j.yrtph.2016.09.029
[Indexed for MEDLINE]

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