<p>The effect of a mesenchymal stem cell conditioned medium fraction on morphological characteristics of hepatocytes in acetaminophen-induced acute liver failure: a preliminary study</p>

Abstract

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% O 2 hc-MSC) and normal (21% O 2 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 O 2 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 O 2 (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.

Biomaterials Functionalized with MSC Secreted Extracellular Vesicles and Soluble Factors for Tissue Regeneration

“…[20] MSC-CM enhances in vitro cell proliferation, [21][22][23] migration, [22,24] angiogenesis, [25] and imparts anti-apoptotic [23,25] and anti-inflammatory [26] effects. In vivo, MSC-CM has demonstrated healing in diverse preclinical indications including cutaneous wounds, [22] Parkinson's disease, [27] liver failure, [28] and myocardial infarction (MI). [29,30] Indeed, significant data indicate that MSC-CM can achieve similar results as direct MSC delivery in various preclinical injury models, [31][32][33] while others report inadequate healing by MSC-CM compared with MSC transplantation.…”

Functional heterogeneity of mesenchymal stem cells from natural niches to culture conditions: implications for further clinical uses

“…In concordance with all these in vitro data, several in vivo studies showed the advantages of hypoxic pre-conditioning in MSC culture in therapeutic terms. In fact, there are studies reporting that the enhanced paracrine effect of MSC after hypoxic treatment would be beneficial to diabetes [164], liver failure [165,166], irradiation-mediated salivary gland damage [167] or anticancer effects [90]. Nevertheless, despite all these potential therapeutic advantages, there are issues which should be resolved.…”

Mesenchymal stromal cells (MSCs) and their exosome in acute liver failure (ALF): a comprehensive review

“…MSCs-conditioned medium (CM) could also modify morphological characteristics of hepatocytes in the ALF model. Meanwhile, secretome achieved by cultivating MSCs with low oxygen content (10%) provoked more prominent hepatoprotective influence, and significantly reduced ALT and AST and also pro-inflammatory cytokines serum levels following injection in vivo [ 153 ]. In another study, Li and coworkers evaluated the therapeutic merits of CM from MSCs co-cultured with hepatocytes in the ALF rat model [ 154 ].…”