Role of B7- H4 molecular in mesenchymal stem cell C3H10 T1/2 transplantation therapy for experimental allergic encephalitis mice models

Abstract

Objective To investigate the role of B7-H4 molecule in C3H10 T1/2 (C3H10) cell transplantation therapy for experimental allergic encephalitis (EAE) mice models from the perspective of pathology. Methods Twenty female C57BL/6 mice were divided into normal group, EAE model group, C3H10 cell group, C3H10-nornal control (NC) cell group, C3H10-short hair (sh)RNA cell group(n=4); EAE models in the later four groups were induced with myelin oligodendrocyte glycoprotein (MOG); C3H10 cells, C3H10-NC cells and C3H10-shRNA cells were transplanted into the mice of the later three groups. The distributions of transplanted cells were observed; the alterations of inflammatory cell infiltration and demyelination were detected by HE staining and Fast- blue staining. Immumofluorescence method was employed to detect the proliferation of astrocytes and microglial cells; B7-H4 molecule expression and effect of knocking down B7-H4 molecule on spinal cord tissue structure and function of EAE mice. Results (1) C3H10 cell transplantation could delay the onset of EAE and alleviate the clinical symptoms: the peak of onset in mice of C3H10 cell group and C3H10-NC cell group was postponed for about 3-5 d as compared with that in EAE model group, and neurological scale scores in the C3H10 cell group and C3H10-NC cell group were obviously decreased as compared with those in EAE model group; knocking down B7-H4 molecule could obviously lower these effects: the peak of onset and neurological scale scores in mice of C3H10-shRNA cell group were closed to those in EAE model group. (2) In the central nervous system, the transplanted cells in the C3H10 cell group, C3H10-NC cell group, C3H10-shRNA cell group mainly distributed in the lesion areas, while little or none transplanted cells existed in the normal tissues. (3) The transplantion of C3H10 in EAE mice could reduce inflammatory cell infiltration, demyelination and gliosis activation and migration; however, after knocking down B7-H4 on C3H10, the inhibition effect was obviously weakened. (4) C3H10 stem cells could influence B7-H4 molecule mediating immune regulation in spinal cord tissues of EAE mice: the B7-H4 expression in the spinal cord tissues of EAE model group was significantly decreased as compared with that in the normal group (P<0.05); the B7-H4 expression in the spinal cord tissues of C3H10 cell group, C3H10-NC cell group was significantly decreased as compared with that in the normal group (P<0.05); the B7-H4 expression in the spinal cord tissues of C3H10-shRNA group was significantly decreased as compared with that in the C3H10 cell group and C3H10-NC cell group (P<0.05). Conclusions C3H10 cells can migrate to the lesion areas and delay the onset or ameliorate symptoms of EAE through a variety of ways. In addition, B7-H4 negative costimulatory molecules in C3H10 cells play important role in immunomodulators of EAE mice models. Key words: Experimental allergic encephalomyelitis; Mesenchymal stem cell; B7-H4