Leiden University Scholarly Publications

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Duijvestein, M.; Wildenberg, M.E.; Welling, M.M.; Hennink, S.; Molendijk, I.; Zuylen, V.L. van; ... ; Hommes, D.W. (2011)

Pretreatment with Interferon-gamma Enhances the Therapeutic Activity of Mesenchymal Stromal Cells in Animal Models of Colitis

Article / Letter to editor
Mesenchymal stromal cells (MSCs) are currently under investigation for the treatment of inflammatory disorders, including Crohn's disease. MSCs are pluripotent cells with immunosuppressive properties. Recent data suggest that resting MSCs do not have significant immunomodulatory activity, but that the immunosuppressive function of MSCs has to be elicited by interferon-gamma (IFN-gamma). In this article, we assessed the effects of IFN-gamma prestimulation of MSCs (IMSCs) on their immunosuppressive properties in vitro and in vivo. To this end, we pretreated MSCs with IFN-gamma and assessed their therapeutic effects in dextran sodium sulfate (DSS)- and trinitrobenzene sulfonate (TNBS)-induced colitis in mice. We found that mice treated with IMSCs (but not MSCs) showed a significantly attenuated development of DSS-induced colitis. Furthermore, IMSCs alleviated symptoms of TNBS-induced colitis. IMSC-treated mice displayed an increase in body weight, lower colitis scores, and better...Show moreMesenchymal stromal cells (MSCs) are currently under investigation for the treatment of inflammatory disorders, including Crohn's disease. MSCs are pluripotent cells with immunosuppressive properties. Recent data suggest that resting MSCs do not have significant immunomodulatory activity, but that the immunosuppressive function of MSCs has to be elicited by interferon-gamma (IFN-gamma). In this article, we assessed the effects of IFN-gamma prestimulation of MSCs (IMSCs) on their immunosuppressive properties in vitro and in vivo. To this end, we pretreated MSCs with IFN-gamma and assessed their therapeutic effects in dextran sodium sulfate (DSS)- and trinitrobenzene sulfonate (TNBS)-induced colitis in mice. We found that mice treated with IMSCs (but not MSCs) showed a significantly attenuated development of DSS-induced colitis. Furthermore, IMSCs alleviated symptoms of TNBS-induced colitis. IMSC-treated mice displayed an increase in body weight, lower colitis scores, and better survival rates compared with untreated mice. In addition, serum amyloid A protein levels and local proinflammatory cytokine levels in colonic tissues were significantly suppressed after administration of IMSC. We also observed that IMSCs showed greater migration potential than unstimulated MSCs to sites within the inflamed intestine. In conclusion, we show that prestimulation of MSCs with IFN-gamma enhances their capacity to inhibit Th1 inflammatory responses, resulting in diminished mucosal damage in experimental colitis. These data demonstrate that IFN-gamma activation of MSCs increases their immunosuppresive capacities and importantly, their therapeutic efficacy in vivo. STEM CELLS 2011;29:1549-1558Show less
Crohn's disease Mesenchymal stem cell Mesenchymal stromal cells Experimental mouse model versus-host-disease tnbs-induced colitis stem-cells ifn-gamma crohns-disease t-cells phase-i mice murine vivo
All authors
Duijvestein, M.; Wildenberg, M.E.; Welling, M.M.; Hennink, S.; Molendijk, I.; Zuylen, V.L. van; Bosse, T.; Vos, A.C.W.; Jonge-Muller, E.S.M. de; Roelofs, H.; Weerd, L. van der; Verspaget, H.W.; Fibbe, W.E.; Velde, A.A.T.; Brink, G.R. van den; Hommes, D.W.
Date
2011-10-31
Journal
STEM CELLS
Volume
29
Issue
10
Pages
1549 - 1558
DOI
doi:10.1002/stem.698