Application of human mesenchymal stem cells cultured in different oxygen concentrations for treatment of graft-versus-host disease in mice.

Human mesenchymal stem cell (MSC) heterogeneity and problems associated with the ex vivo expansion of MSC are linked with the failure of MSC clinical trials. In this study, we compared the effect of MSCs cultured in different oxygen concentrations on GVHD in mice to elucidate whether hypoxia improves the immunosuppressive capacity of MSCs. Hypoxia increased the proliferative activity and the expression of several stemness and chemokine genes, such as KLF4, OCT4, C-MYC, CCL2, and CXCL10. Mice that received MSCs cultured in normoxia or hypoxia showed alleviated symptoms of GVHD and increased survival times. However, there was no significant difference in survival rates between mice that received MSCs cultured in normoxia and hypoxia. These data suggest that hypoxic culture is a useful method for maintaining and obtaining MSCs used for cell therapy and that the therapeutic potential of MSCs cultured in hypoxia warrants further investigation.