The effect of a mesenchymal stem cell conditioned medium fraction on morphological characteristics of hepatocytes in acetaminophen-induced acute liver failure: a preliminary study
Received 28 November 2018
Accepted for publication 26 April 2019
Published 19 July 2019 Volume 2019:11 Pages 89—96
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Dr Gerry Lake-Bakaar
Andrey Temnov1,2, Konstantin Rogov3,4, Vitaliy Zhalimov,1 Popov Igor,2 Stanislav Pekov,2 Augustinus Bader,5 Alla Sklifas,1 Shibashish Giri5,6
1Department of Biology, Institute of Cell Biophysics of the Russian Academy of Sciences, Pushchino, Russia; 2Department of Biotechnology, Moscow Institute of Physics and Technology, Dolgoprudny, Russia; 3Department of Clinical Morphology, Research Institute of Human Morphology, Moscow, Russia; 4Department of Pathomorphology, Peoples’ Friendship University of Russia, Moscow, Russia; 5Applied Stem Cell Biology and Cell Technology, Biomedical and Biotechnological Center, Leipzig University, Leipzig, Germany; 6Department of Plastic and Hand Surgery, University Hospital Rechts der Isar, Munich Technical University, Munich, Germany
Background: In our studies, it was shown that the effectiveness of the conditioned medium obtained by cultivating mesenchymal stem cells depends on the microenvironment conditions used to cultivate the cells. It was demonstrated that the conditioned medium obtained by culturing cells with low oxygen content (10%) has a much more pronounced protective effect.
Methods: Protein compositions obtained from MSCs cultured under hypoxic (10% O2 hc-MSC) and normal (21% O2 nc-MSC) conditions were used to treat acute liver failure (ALF) induced in mice by acetaminophen injection. Thus, we obtained fractions normalized by volume, which predominantly contained proteins with masses > 50, 50-30, 30-10, and 10-3 kDa.
Results: The data from biochemical studies have shown that only fractions from 10 to 30 kDa (hcMSC and ncMSC) significantly reduced the level of liver enzymes in the beginning of the acute period after acetaminophen administration. Mass spectrometry analysis of the proteins contained in the isolated fractions showed a sharp increase in the protein levels in the 10-30 kDa hcMSC fraction as compared with that in 10-30 kDa ncMSCs. The composition obtained from MSCs cultured at lower O2 level (fraction 10-30 kDa hcMSC) was shown to be more potent than the composition prepared from normoxic cells.
Conclusion: The results have shown that a composition obtained by culturing the cells under a reduced content of O2 (10%), significantly improves the biochemical parameters, and histological arrester reduces the degree of inflammation and stimulates regenerative processes in liver, compared to both the control group and group treated with the composition that was obtained by culturing the cells under normal oxygen content.
Keywords: acute hepatic failure, stem cells, condition media, galectin-1, mass spectrometry
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