Human umbilical cord-derived mesenchymal stem cells in acute liver injury: Hepatoprotective efficacy, subchronic toxicity, tumorigenicity, and biodistribution.
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 × 108cells/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.
Department of Experimental Animal Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
Jun-Won
JW
Yun
Graduate School of Translational Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
Jae Hun
JH
Ahn
Department of Experimental Animal Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
Euna
E
Kwon
Department of Experimental Animal Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
Seung-Hyun
SH
Kim
Department of Experimental Animal Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
Hanna
H
Kim
Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea.
Ja-June
JJ
Jang
Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea.
Woo Ho
WH
Kim
Biotechnology Research Institute, Hurim BioCell Co. Ltd., Seoul, Republic of Korea.
Ji Hyang
JH
Kim
Biotechnology Research Institute, Hurim BioCell Co. Ltd., Seoul, Republic of Korea.
Su-Youne
SY
Han
Biotechnology Research Institute, Hurim BioCell Co. Ltd., Seoul, Republic of Korea.
Jin Tac
JT
Kim
Laboratory of Stem Cell Biology, Division of Biotechnology, Department of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
Jong-Hoon
JH
Kim
Department of General Surgery, Ajou University School of Medicine, Suwon, Republic of Korea.
Wookhwan
W
Kim
Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Republic of Korea.
Seung-Yup
SY
Ku
Biotechnology Research Institute, Hurim BioCell Co. Ltd., Seoul, Republic of Korea. Electronic address: brokdo@nuri.net.
Byung-Rok
BR
Do
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.
Byeong-Cheol
BC
Kang
D000818:Animals; D002251:Carbon Tetrachloride; D006801:Humans; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000473:pathology* / Q000628:therapy*; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D014470:Umbilical Cord / Q000166:cytology*
D002251:Carbon Tetrachloride
Biodistribution; Liver injury; Toxicity; Tumorigenicity; Umbilical cord-derived mesenchymal stem cells