The preliminary study for the role of B7-H4 for the treatment of experimental autoimmune encephalomyelitis by mesenchymal stem cell C3H10 T1/2 transplantation

Objective To investigate the role of the negative co-stimulatory molecule B7-H4 in mesenchymal stem cell line C3H10 T1/2 (C3H10) in the treatment of experimental allergic encephalitis(EAE). Methods ①The lentiviral vectors with mouse B7-H4 target shRNA were transfected into mouse mesenchymal stem cell (C3H10-shRNA); the flow cytometry was used to detect the proliferation of splenocyte that was co-cultured with C3H10 cell.②EAE mice models were immunized with peptide MOG35-55 in complete Freund’s adjuvant (CFA); C57BL/6 mice(n=50) were divided into Sham-operated group, EAE model group, C3H10 cell group, C3H10-NC cell group, and C3H10-shRNA cell group. Through HE and luxol fast blue staining to observe the pathologic changes of mice. Immunohistochemistry was used to label B7-H4. Combining with the neural function defect score , the effect of transplantation of mice with different cells was evaluated. Results ①By knocking down B7-H4 on C3H10, the inhibitory effect of C3H10 on splenocyte proliferation was partly revised; ②Transplantation of C3H10 into EAE mice can decrease and delay the attack. The onset time of the attack, the neural function defect score, the inflammatory cell infiltration, the demyelination and the number of B7-H4 positive cells of the C3H10-shRNA cell group was between EAE model group and other control groups. Conclusions The treatment of EAE by C3H10 transplantation is safe and effective. The co-inhibitor molecule B7-H4 expressed on C3H10 cell involved in the effect of the treatment of EAE by C3H10 transplantation. Key words: Experimental allergic encephalitis; Mesenchymal stem cell; B7-H4; C3H10 T1/2