The Effect Of Bone Marrow Mesenchymal Stem Cells Transduced With Inducible Costimulator Gene On Acute Graft-versus-host Disease After Experimental Stem Cell Transplantation In Mice

In the present project, the effects of mMSC, a bone marrow derivedmesenchymal stem cells (MSCs) transduced with inducible costimulator (ICOS)-geneusing an adenoviral vector, on murine aGVHD model were investigated. Recipient micewere injected with mMSC^-ICOS, mMSCs, mMSC^-EGFP, ICOS-Ig fusion protein or the diluent(control), respectively. About95%mMSCs expressed ICOS protein after transfection withAd5/f11b-ICOS-EGFP and all cells retained their biological characteristics after adenovirustransfection. Survival in recipients of mMSC^-ICOS was significantly higher than othergroups (P＜0.05). The lower mortality in recipients of mMSC^-ICOSwas related tomMSC^-ICOScan reduce the total number of T cells in aGVHD environment, especially forCD4⁺T cells, and the apoptosis of CD4⁺and CD8+T cells was significantly higher inmMSC^-ICOSgroup on day3. We can also find that the higher serum levels of IL-4,IL-10and lower levels of IFN-γ,IL-2,IL-17A,IL-12in mMSC^-ICOSgroup, as well as inducingexpression of GATA-3, STAT6, Foxp3transcription factors while inhibiting expressionof T-bet, STAT4, ROR-γt in spleen.These date suggest that mMSC^-ICOS is a moreprospective strategy for acute GVHD prevention, which is associated with regulation of theTh1/Th2/Th17balance in the early stage of acute GVHD. The current study may surve asthe basis of new strategy for prevention and treatment of aGVHD.