Inducible Co-stimulator Gene Modified Bone Marrow Mesenchymal Stem Cells Can Attenuate The Severity Of Acute Graft-versus-host Disease After Experimental Allogeneic Stem Cell Transplantation In Mice

Objective: We use mICOS-transduced mMSCs to intervene aGVHD in mouse model and investigate its role in aGVHD. Methods:Ad5/F11b-mICOS-EGFP transduce mMSCs, and identify their biological characters. Lethally irradiated BALB/c recipients received allogeneic BM cells and spleen cells of C57BL/6 origin, with mMSC-ICOS,mMSC-EGFP or ICOS-Ig fusion protein intervention (2×105 mMSC-ICOS or mMSC-EGFP were injected transveinously on day 0, ICOS-Ig fusion protein was injected intraperitaoneally on day 0,2,4,8 at a dose of 100μg ),GVHD group was a control group. Proliferation, apoptosis and Treg cells of MNCs from spleen were detected by FCAS on 7th and 14th day after transplantation, cytokines of PB and transcription factors were detected by ELISA or RT-PCR on 14th day after transplantation. Results: mMSC-ICOS could attenuate the severity of aGVHD and prolong survive. mMSC-ICOS promoted apoptosis but not proliferation of MNCs from spleen, and tip the bias of Th1 to Th2. Treg cells were not induced by mMSC-ICOS. Conclusion: mMSC-ICOS can attenuate the severity of aGVHD in mouse and prolong survive. Its beneficial effects on aGVHD may be related to promoting apoptosis of T cells and altering the polarization state of T helper cells.