Inflammation Differentially Modulates the Biological Features of Adult Derived Human Liver Stem/Progenitor Cells

Autor: Mustapha Najimi, Vera Rogiers, Etienne Sokal, Hoda El-Kehdy, Laurence Lagneaux, Joery De Kock, Mehdi Najar, Makram Merimi, Douaa Moussa Agha
Přispěvatelé: UCL - SSS/IREC/PEDI - Pôle de Pédiatrie, UCL - (SLuc) Service de gastro-entérologie et hépatologie pédiatrique, Pharmaceutical and Pharmacological Sciences, Experimental in vitro toxicology and dermato-cosmetology, Vriendenkring VUB, Department of Bio-engineering Sciences
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Cells
Volume 9
Issue 7
Cells, Vol. 9, no. 7, p. 1640 [1-20] (2020)
Cells, 9 (7
Cells, Vol 9, Iss 1640, p 1640 (2020)
ISSN: 2073-4409
DOI: 10.3390/cells9071640
Popis: 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&ndash
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.
Databáze: OpenAIRE