Human umbilical cord mesenchymal stromal cells rescue mice from acetaminophen-induced acute liver failure

Z. Liu, F. Meng, C. Li, X. Zhou, X. Zeng, Y. He, R.J. Mrsny, M. Liu, X. Hu, J.-F. Hu, T. Li

Research output: Contribution to journalArticle

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Abstract

Background aims: Acute liver failure (ALF), a life-threatening disease characterized by the sudden loss of hepatic function, can occur after an accidental or intentional acetaminophen overdose. Methods: With the use of an ALF mouse model, we examined both the preventive and therapeutic potential of intravenously administered human umbilical cord-derived mesenchymal stromal cells (hUCMSCs). Primary hUCMSCs were purified from freshly collected full-term umbilical cords and intravenously transplanted into BALB/c mice either before and after ALF induced by acetaminophen intoxication. We found that hUCMSCs significantly improved survival rates and relative liver weight of mice in both pre-ALF and post-ALF animals. Correspondingly, serum levels of markers that reflect hepatic injury (ie, aspartate aminotransferase, alanine aminotransferase and total bilirubin) were significantly attenuated in the group receiving hUCMSC therapy. Results: Mechanistically, we found that the protective potential of intravenously administered hUCMSCs was mediated by paracrine pathways that involved antioxidants (glutathione, superoxide dismutase), the reduction of inflammatory agents (tumor necrosis factor-α, interleukin-6) and elevated serum levels of hepatocyte growth factor. Conclusions: Through these paracrine effects, intravenously administered hUCMSCs reduced hepatic necrosis/apoptosis and enhanced liver regeneration. Thus, our data demonstrate that intravenously administered hUCMSCs may be useful in the prevention or treatment of acetaminophen-induced ALF.
Original languageEnglish
Pages (from-to)1207-1219
Number of pages13
JournalCytotherapy
Volume16
Issue number9
Early online date7 Aug 2014
DOIs
Publication statusPublished - Sep 2014

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Acute Liver Failure
Umbilical Cord
Acetaminophen
Mesenchymal Stromal Cells
Liver
Liver Regeneration
Hepatocyte Growth Factor
Cell- and Tissue-Based Therapy
Aspartate Aminotransferases
Alanine Transaminase
Bilirubin
Superoxide Dismutase
Glutathione
Interleukin-6
Necrosis
Tumor Necrosis Factor-alpha
Antioxidants
Biomarkers
Apoptosis
Weights and Measures

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Human umbilical cord mesenchymal stromal cells rescue mice from acetaminophen-induced acute liver failure. / Liu, Z.; Meng, F.; Li, C.; Zhou, X.; Zeng, X.; He, Y.; Mrsny, R.J.; Liu, M.; Hu, X.; Hu, J.-F.; Li, T.

In: Cytotherapy, Vol. 16, No. 9, 09.2014, p. 1207-1219.

Research output: Contribution to journalArticle

Liu, Z, Meng, F, Li, C, Zhou, X, Zeng, X, He, Y, Mrsny, RJ, Liu, M, Hu, X, Hu, J-F & Li, T 2014, 'Human umbilical cord mesenchymal stromal cells rescue mice from acetaminophen-induced acute liver failure', Cytotherapy, vol. 16, no. 9, pp. 1207-1219. https://doi.org/10.1016/j.jcyt.2014.05.018
Liu, Z. ; Meng, F. ; Li, C. ; Zhou, X. ; Zeng, X. ; He, Y. ; Mrsny, R.J. ; Liu, M. ; Hu, X. ; Hu, J.-F. ; Li, T. / Human umbilical cord mesenchymal stromal cells rescue mice from acetaminophen-induced acute liver failure. In: Cytotherapy. 2014 ; Vol. 16, No. 9. pp. 1207-1219.
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