Article Text

other Versions

PDF
Functional, molecular and proteomic characterization of bone marrow mesenchymal stem cells in rheumatoid arthritis
  1. Maria-Christina Kastrinaki (kastrinaki{at}med.uoc.gr)
  1. University of Crete School of Medicine, Greece
    1. Prodromos Sidiropoulos (sidiropp{at}med.uoc.gr)
    1. University of Crete School of Medicine, Greece
      1. Stephan Roche
      1. Institut de Genetique Humaine, Montpellier, France
        1. Jochen Ringe
        1. Charite Universitatsmedizin, Berlin, Germany
          1. Sylvain Lehmann
          1. Institut de Genetique Humaine, Montpellier, France
            1. Heraklis Kritikos
            1. University of Crete School of Medicine, Greece
              1. Virginia Maria Vlahava
              1. University of Crete School of Medicine, Greece
                1. Bruno Delorme
                1. University Francois Rabelais, Faculty of Medicine, Tours, France
                  1. George Eliopoulos (gel1{at}otenet.gr)
                  1. University of Crete School of Medicine, Greece
                    1. Christian Jorgensen
                    1. Hopital Lapeyronie, Service d'Immuno-Rhumatologie, Montpellier, France
                      1. Pierre Charbord
                      1. University Francois Rabelais, Faculty of Medicine, Tours, France
                        1. Thomas Häupl
                        1. Charite Universitatsmedizin, Berlin, France
                          1. Dimitrios T. Boumpas (boumpasd{at}med.uoc.gr)
                          1. University of Crete School of Medicine, Greece
                            1. Helen A. Papadaki (epapadak{at}med.uoc.gr)
                            1. University of Crete School of Medicine, Greece

                              Abstract

                              Objective: Bone marrow (BM) mesenchymal stem cells (MSCs) are being considered as potential therapeutic agents in various inflammatory autoimmune diseases for their tissue-repair and anti-inflammatory tissue-protective properties. This study investigates the reserves and function, the molecular and proteomic profile and the differentiation potential of BM MSCs in patients with active rheumatoid arthritis (RA).

                              Methods: We have evaluated the frequency of MSCs in the BM mononuclear cell fraction using a limiting dilution assay, the proliferative/clonogenic potential and the capacity of cells to differentiate towards the osteogenic/chondrogenic/adipogenic lineages using appropriate culture conditions. We have also assessed the molecular and proteomic characteristics in terms of inflammatory cytokine gene and protein expression, the relative telomere length and the survival characteristics of BM MSCs.

                              Results: MSCs from RA patients (n=26) and age-/sex-matched healthy individuals (n=21) were similar in frequency, differentiation potential, survival, immunophenotypic characteristics, and protein profile. Patient MSCs, however, had impaired clonogenic and proliferative potential in association with premature telomere length loss. Transcriptome analysis revealed differential expression of genes related to cell adhesion processes and cell cycle progression beyond the G1 phase. Previous treatment with methotrexate, corticosteroids, anti-cytokine and biological agents or other disease-modifying anti-inflammatory drugs did not correlate with the clonogenic and proliferative impairment of BM MSCs.

                              Conclusion: In spite of some restrictions related to the impaired clonogenic and proliferative potential, our findings support the use of autologous BM MSCs in RA and may have important implications for the ongoing efforts to repair tissue injury commonly seen in the course of the disease.

                              • bone marrow
                              • focal adhesion
                              • mesenchymal stem cells
                              • rheumatoid arthritis
                              • telomere length

                              Statistics from Altmetric.com

                              • web only appendices 67/6/741

                                Request permissions

                                If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.