ROLE OF INFLAMMATION IN MODULATING GRAFT TOLERANCE INDUCED BY MESENCHIMAL STEM CELLS
Abstract number: P-S-471
Giusti1 B., Mazzanti2 B., Rossi1 L., Lapini1 I., Sestini1 I., Magi1 A., Torricelli3 F., Saccardi4 R., Fimiani5 M., Abbate1 R.
11Department of Medical and Surgical Critical Care 22Department of Haematology, University of Florence 33Genetic Diagnostic Unit, Azienda Ospedaliero Universitaria Careggi 44Hematology Unit, Careggi Hospital 55Department of Clinical Medicine and Immunological Sciences, Section of Dermatology, University of Siena, Florence, Italy
How-to-cite Giusti B, Mazzanti B, Rossi L, Lapini I, Sestini I, Magi A, Torricelli F, Saccardi R, Fimiani M, Abbate R. ROLE OF INFLAMMATION IN MODULATING GRAFT TOLERANCE INDUCED BY MESENCHIMAL STEM CELLS. J Thromb Haemost 2007; 5 Supplement 2: P-S-471
Abstract
Introduction: Mesenchymal stem cells (MSCs) possess immunomodulatory properties and inhibit T-cell proliferation in vitro; this suggests that MSCs may be used for the prevention and treatment of graft-versus-host disease in organ transplantation. In vitro evidences suggested inflammatory environment could modulate the behaviour of MSC.
Methods: We performed a case-control study to assess the effect of intravenous administration of MSCs in rats undergone skin allograft transplantation. The experimental design included 4 arms: group A, rats receiving only skin transplantation; group B, skin transplantation and cyclosporine A (CyA) immunosuppressive therapy; group C, skin transplantation, CyA and endovenous infusion of donor MSCs; group D, skin transplantation and MSCs infusion. For each arm, we evaluated the timing of allograft rejection and expression of 6 genes involved in immunomodulatory effect by real-time PCR.
Results: Rats of group C had significantly higher median value of skin allograft rejection: 30 (range 15-30) vs 18, 20 and 13 days for group A, B, and D, respectively.
IFN-gamma and IL-2 gene expression was significantly different among the 4 groups (p<0.0001 and p=0.023, respectively). IFN-gamma mRNA levels were lower in group B (p=0.004) and group D (p=0.002) in comparison to group A. TNF-alpha mRNA gene expression was lower in B and more markedly in C group, in comparison to group A. IL-10 mRNA levels were higher in group C in comparison to the other 3 groups (p=0.06). IDO mRNA levels in group B were lower than in both group A (p= 0.001) and group C (p=0.001). TGF-beta mRNA levels were lower in CyA+MSCs group than in CyA (p=0.002), untreated (p=0.019), and MSCs (p=0.02) groups.
Conclusions: Our data suggest an immunogenic role of MSC per sè, whereas MSC may significantly improve the graft tolerance in CyA treated immunodeficient animals. Inflammatory molecules and in particular TNF-alpha seem to play a pivotal role in modulating this phenomenon.
