(P 130) Does Administration of Immunosuppressive Drugs Impact on the Immunomodulatory Properties of Mesenchymal Stem Ceils (MSC): Insights from an In vitro Study

• Published in: Tissue engineering. Part A 2008-05, Vol.14 (5), p.840-840
• Main Authors: Poncelet, A J, Nizet, Y, Lecuivre, C, Vercruysse, J, Gianello, P
• Format: Article
• Language: English
• ISSN: 1937-3341; 1937-335X

Background: Mesenchymal stem cells (MSC) down-modulate immune responses in vitro and clinical studies currently test the role of allogeneic MSC in immunosuppressed patients suffering from graft versus host disease (GVHD). We tested in vitro the interaction of different immunosuppressive drugs (IS) on the immuno-modulatory properties of MSC. Methods: Both calcineurin inhibitors: cyclosporine (CsA) and tacrolimus (Tac), and mTOR inhibitors: sirolimus (Si) and ever-olimus (Ev) were tested. MSC proliferation was assessed on day 5 & 7. For in vitro experiments, the effect of IS drugs on the immune modulation by MSC was measured in proliferation assays of modified mixed lymphocyte reaction where MSC were added (ratio 1:2) with decreasing concentration of IS drugs (C100 to C0). Results: On day 5, no significant difference in proliferation was noticed among IS drugs. On day 7 of culture, all IS drugs except tacrolimus significantly decreased cell proliferation compared to IS-free culture medium (CsA, -43.6%; Si, -14%, Ev, -17%). In dose-dependant PBMC-MSC co-cultures, the immunomodulatory properties of allogeneic MSC were maintained independantly of the concentration of IS drug used. At C50 for Tac (5 ng/ml) and Si (0.3 ng/ml), the downmodulation by MSC was still present since the degree of inhibition, for a 1:2 MSC/PBMC ratio, was 96% and 94%, respectively. Conclusions: The concomitant use of immunosuppressive drugs significantly interacts on the proliferation of MSC in vitro. Among their class, Tacrolimus and Sirolimus were the drugs with the least interaction and at C50 neither had detrimental effect on the immuno-modulatory properties of MSC.