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Lipopolysaccharide preconditioning of adipose-derived stem cells improves liver-regenerating activity of the secretome
INTRODUCTION: Growing recognition of paracrine mechanisms in stem cell plasticity has resulted in considerable interest in stem cell-derived secretome. The aim of this study was to investigate the effects of lipopolysaccharide (LPS) preconditioning on the composition and hepatic regenerative activit...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4416308/ https://www.ncbi.nlm.nih.gov/pubmed/25890074 http://dx.doi.org/10.1186/s13287-015-0072-7 |
Sumario: | INTRODUCTION: Growing recognition of paracrine mechanisms in stem cell plasticity has resulted in considerable interest in stem cell-derived secretome. The aim of this study was to investigate the effects of lipopolysaccharide (LPS) preconditioning on the composition and hepatic regenerative activity of adipose-derived stem cell (ASC) secretome. METHODS: Conditioned medium (CM) and LPS-CM were obtained after culturing human ASCs without or with low-dose LPS (0.5 ng/mL) for 24 hours. Untreated and thioacetamide-treated mouse AML12 hepatocytes were incubated for 24 hours with the control medium, LPS (0.5 ng/mL), CM, and LPS-CM and then cell viabilities were compared. CM and LPS-CM were also intravenously administered to partially hepatectomized mice, and their effects on liver regeneration were assessed by using liver weight measurements, immunohistochemistry, and Western blotting. RESULTS: In the in vitro experiments, LPS preconditioning of ASCs enhanced the mRNA expression levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), hepatocyte growth factor, and vascular endothelial growth factor, which evoke inflammatory response or liver regeneration. LPS-CM significantly promoted thioacetamide-damaged AML12 cell viability compared with CM-incubated cells and the control cells (77%, 69%, and 65% P <0.05). In the in vivo experiment, LPS-CM infusion into the partially hepatectomized mice significantly reduced serum IL-6 and TNF-α levels compared with the other groups (P <0.05) on days 1 and 2 after partial hepatectomy. Moreover, LPS-CM infusion enhanced liver regeneration (based on the liver weight changes at day 7 after partial hepatectomy, 3.73% versus 3.22% in the CM group; P <0.05) and significantly reduced the elevated serum levels of aspartate transaminase and alanine transaminase (at day 1, P <0.05). CONCLUSIONS: Our results suggest that LPS preconditioning effectively stimulates ASCs to produce the secretome beneficial to hepatic regeneration. Thus, optimizing ASC secretome profile by LPS preconditioning could be a promising approach to treat liver diseases by using stem cells. |
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