Phenotypic, genotypic and functional characterization of mesenchymal stem cells from synovial membrane compared with bone marrow

Mesenchymal stem cells (MSC) are progenitor cells of mesodermal lineages that are present in different tissues such as the fat pads and the bone marrow (BM) but also in the cartilage and the synovial membrane (SM). The aim of this study was to better characterize BM-derived and SM-derived MSC and discriminate between the two tissue sources.

BM-MSC and SM-MSC were compared for the expression of cell surface markers and induction of MHC class I and class II molecules by interferon (IFN)-α2, IFN-β and IFN-γ. Functional characterization was assessed through their differentiation potential towards chondrocytes and osteoblasts using quantitative RT-PCR, and their immunosuppressive properties by mixed lymphocyte reaction and indoleamine 2,3-dioxygenase activity. Using macroarray technology, the expression of 268 genes was monitored in four samples from BM-derived and SM-derived MSC.

BM-derived and SM-derived MSC were shown to express CD44, CD73, CD90 and CD105 in the same range and to respond to IFN stimulation. We showed that IFN-β, IFN-α2 and IFN-γ are able to stimulate the expression of MHC class I and class II molecules on the MSC surface from both origins. Using quantitative analysis, we demonstrated similar differentiation capacities (osteogenesis and chondrogenesis induction) for BM-derived or SM-derived MSC. Moreover, our data are the first to show the same immunosuppressive features in mixed lymphocyte reaction (>90% of T-cell proliferation inhibition) and similar expression of indoleamine 2,3-dioxygenase in BM-derived and SM-derived MSC. Nevertheless, the macroarray analysis shows a statistically significant discrimination between SM-derived and BM-derived MSC, in particular inflammatory cytokine as IL6 and IL8 were upregulated in synoviocytes compared with BM-MSC. Validation in terms of expression of specific proteins is being undertaken.

Altogether, the data indicate that BM-MSC and SM-MSC shared multiple phenotypic and functional properties. However, the genomic signature permits one to discriminate the MSC originating from the two different tissues.

Affiliations

1. INSERM U475, Montpellier, France
   • F Djouad
   • , D Noël
   • , P Plence
   • , C Bony
   • , F Apparailly
   •  & C Jorgensen
2. CNRS UMR 5124, University of Montpellier II, Montpellier, France
   • G Uzé
3. Charité Hospital, Berlin, Germany
   • T Haüpl
   •  & C Jorgensen

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