IFN-γ gene loaded human umbilical mesenchymal stromal cells targeting therapy for Graft-versus-host disease

Graft-versus-host disease (GVHD) is a frequent complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). The application of mesenchymal stromal cells (MSCs) to treat GVHD patients refractory to initial steroid treatment has led to impressive results. In this study, we explored the potential of human umbilical mesenchymal stem cells (HUMSCs) transfected with the IFN-γ gene of human (h)/mice (m) (HUMSCs + Ad-h/mIFN-γ) carried by a recombinant adenoviral vector in the prevention and treatment of GVHD. We demonstrated that HUMSCs + Ad-h/mIFN-γ efficiently suppressed T lymphocyte proliferation and activation, induced G1 cell cycle arrest and apoptosis in vitro. To assess the in vivo efficacy of HUMSCs + Ad-h/mIFN-γ, Balb/c mice were induced to develop GVHD symptoms by tail vein injection of C57BL/6 splenocytes after irradiation. Weight, hair, survival, hemogram, and chimera condition of GVHD model mice were monitored before and after treatment, respectively. The results showed that HUMSCs + Ad-h/mIFN-γ reduced GVHD's incidence and severity on the model mice and provided a significant survival benefit. In conclusion, this study may provide validated evidence that the introduction of IFN-γ into HUMSCs would help ameliorate GVHD after allo-HSCT.