Makram Merimi1, Laurence Lagneaux2, Catherine A Lombard3, Douâa Moussa Agha1, Dominique Bron1, Philippe Lewalle1, Nathalie Meuleman1, Mustapha Najimi3, Etienne M Sokal3, Mehdi Najar4,5. 1. Laboratory of Experimental Hematology, Jules Bordet Institute, Université Libre de Bruxelles, 1000, Brussels, Belgium. 2. Laboratory of Clinical Cell Therapy, Jules Bordet Institute, Université Libre de Bruxelles, 1070, Brussels, Belgium. 3. Laboratory of Pediatric Hepatology and Cell Therapy, Institut de Recherche Expérimentale Et Clinique (IREC), Université Catholique de Louvain, 1200, Brussels, Belgium. 4. Osteoarthritis Research Unit, University of Montreal Hospital Research Center (CRCHUM), Montreal, QC, H2X 0A9, Canada. mnajar@ulb.ac.be. 5. Department of Medicine, University of Montreal, Montreal, QC, H2X 0A9, Canada. mnajar@ulb.ac.be.
Abstract
OBJECTIVE: One of the main challenges in liver cell therapy is the replacement of damaged cells and the induction of a tolerogenic microenvironment to promote graft acceptance by the recipient. Adult-derived human liver stem/progenitor cells (ADHLSCs) are currently evaluated at the clinical levels as a promising pro-regenerative and immune-modulatory tool. The expression profile of several immunological molecules may influence the local immune-inflammatory response and, therefore, modulate the tissue healing process. To increase the quality and safety of ADHLSCs before transplantation requires an appropriate analysis and characterization of their pattern expression of immune-inflammatory-associated molecules. METHODS: The expression of 27 molecules belonging to T-cell co-stimulatory pathway, CD47 partners, Ikaros family, CD300 family and TNF family were analyzed using flow cytometry. We compared their expression profiles to PBMCs, hepatocytes and ADHLSCs in both expansion and after hepatogenic differentiation culture conditions. RESULTS: This original immuno-comparative screening revealed that liver cell populations do not constitutively present significant immunological pattern compared to PBMCs. Moreover, our findings highlight that neither the expansion nor the hepatogenic differentiation induces the expression of immune-inflammatory molecules. The detailed expression characteristics (percentage of positive cells and median fluorescence intensity) of each molecule were analyzed and presented. CONCLUSION: By analyzing 27 relevant molecules, our immuno-comparative screening demonstrates that ADHLSCs keep a non-immunogenic profile independent of their expansion or hepatogenic differentiation state. Accordingly, the immunological profile of ADHLSCs seems to support their safe and efficient use in liver tissue therapeutic repair strategy.
OBJECTIVE: One of the main challenges in liver cell therapy is the replacement of damaged cells and the induction of a tolerogenic microenvironment to promote graft acceptance by the recipient. Adult-derived human liver stem/progenitor cells (ADHLSCs) are currently evaluated at the clinical levels as a promising pro-regenerative and immune-modulatory tool. The expression profile of several immunological molecules may influence the local immune-inflammatory response and, therefore, modulate the tissue healing process. To increase the quality and safety of ADHLSCs before transplantation requires an appropriate analysis and characterization of their pattern expression of immune-inflammatory-associated molecules. METHODS: The expression of 27 molecules belonging to T-cell co-stimulatory pathway, CD47 partners, Ikaros family, CD300 family and TNF family were analyzed using flow cytometry. We compared their expression profiles to PBMCs, hepatocytes and ADHLSCs in both expansion and after hepatogenic differentiation culture conditions. RESULTS: This original immuno-comparative screening revealed that liver cell populations do not constitutively present significant immunological pattern compared to PBMCs. Moreover, our findings highlight that neither the expansion nor the hepatogenic differentiation induces the expression of immune-inflammatory molecules. The detailed expression characteristics (percentage of positive cells and median fluorescence intensity) of each molecule were analyzed and presented. CONCLUSION: By analyzing 27 relevant molecules, our immuno-comparative screening demonstrates that ADHLSCs keep a non-immunogenic profile independent of their expansion or hepatogenic differentiation state. Accordingly, the immunological profile of ADHLSCs seems to support their safe and efficient use in liver tissue therapeutic repair strategy.
Authors: Marcus Mühlbauer; Martin Fleck; Christian Schütz; Thomas Weiss; Matthias Froh; Christian Blank; Jürgen Schölmerich; Claus Hellerbrand Journal: J Hepatol Date: 2006-06-16 Impact factor: 25.083