Abstract
The progression of mesenchymal stem cell-based therapy from concept to cure closely depends on the optimization of conditions that allow a better survival and favor the cells to achieve efficient liver regeneration. We have previously demonstrated that adult-derived human liver stem/progenitor cells (ADHLSC) display significant features that support their clinical development. The current work aims at studying the impact of a sustained pro-inflammatory environment on the principal biological features of ADHLSC in vitro. METHODS: ADHLSC from passages 4–7 were exposed to a cocktail of inflammatory cytokines for 24 h and 9 days and subsequently analyzed for their viability, expression, and secretion profiles by using flow cytometry, RT-qPCR, and antibody array assay. The impact of inflammation on the hepatocytic differentiation potential of ADHLSC was also evaluated. RESULTS: ADHLSC treated with a pro-inflammatory cocktail displayed significant decrease of cell yield at both times of treatment while cell mortality was observed at 9 days post-priming. After 24 h, no significant changes in the immuno-phenotype of ADHLSC expression profile could be noticed while after 9 days, the expression profile of relevant markers has changed both in the basal conditions and after inflammation treatment. Inflammation cocktail enhanced the release of IL-6, IL-8, CCL5, monocyte-chemo-attractant protein-2 and 3, CXCL1/GRO, and CXCL5/ENA78. Furthermore, while IP-10 secretion was increased after 24 h priming, granulocyte macrophage colony-stimulating factor enhanced secretion was noticed after 9 days treatment. Finally, priming of ADHLSC did not affect their potential to differentiate into hepatocyte-like cells. CONCLUSION: These results indicate that ADHLSCs are highly sensitive to inflammation and respond to such signals by adjusting their gene and protein expression. Accordingly, monitoring the inflammatory status of patients at the time of cell transplantation, will certainly help in enhancing ADHLSC safety and efficiency.
Highlights
Mesenchymal stem cells (MSC) represent a fibroblast-like cell population that displays a potent ability to differentiate and to modulate both adaptive and innate immune systems [1]
To gain insights regarding the behavior of adult-derived human liver stem/progenitor cells (ADHLSC) in inflammatory pathological conditions and the mechanisms by which such cells cooperate with inflammation, we studied in vitro the impact of sustained pro-inflammatory environment on culture expanded ADHLSC as well as after hepatocytic differentiation
We evaluated the impact of inflammation on the yield of ADHLSC
Summary
Mesenchymal stem cells (MSC) represent a fibroblast-like cell population that displays a potent ability to differentiate and to modulate both adaptive and innate immune systems [1]. These undifferentiated and non-hematopoietic cells have received much interest in regenerative medicine. Extensive clinical trials using culture expanded MSC are currently exploring their therapeutic potential in humans [2]. A clinical improvement was noticed in most of the studies, the failure to track these cells in situ obviously supported paracrine-mediated effects. Active rejection and/or letting host cells to subsequently ameliorate injury and accelerate repair, could explain the documented post-transplantation effects. The progression of MSC-based therapeutic approach from concept to cure closely depends on the optimization of specific experimental conditions that allow a better survival and favor the transplanted MSC to achieve efficient tissue regeneration
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