Background: Despite the effectiveness of skin autotransplantation, the high degree of immunogenicity of skin precludes the general use of allogeneic skin grafts. Systemic immunosuppression is generally felt to be inappropriate for isolated skin grafts. This study examines the potential to create an allogeneic skin transplant that delays rejection by inducing localized immunosuppression. Specifically, IDO (indoleamine 2 3-dioxygenase) expressing fibroblasts are introduced into the dermis and subcutaneous area of donor subjects to provide a tryptophan-depleted environment and therefore local immunosuppression toward the graft.
Method: 4-days post-injection of the cells; grafts with regular and IDO fibroblast were transplanted to allogeneic recipients and monitored until graft rejection. To investigate any possible cumulative effect of multiple injections on the survival rate of grafts, cells are injected at the different time point (days 0,3,6) to the same area and a 6mm graft was harvested from that region and transplanted to the allogeneic subjects.
Results: Skin transplantation studies demonstrate that IDO expressing grafts remain viable for significantly longer than control allogeneic grafts (p=0.01). Following 3-times injection of the IDO cells to the allogeneic full-thickness graft, average survival graft rate in IDO group increased up to 35-days in comparison to 13-days for the control group.
Conclusion: These data suggest that local immunosuppression can be provided by the delivery of IDO-expressing fibroblasts in allogeneic skin transplantation. The potential of this research goes far beyond the promising role for skin transplantation. This “cell-based” approach to localized immunosuppression can also provide potential opportunities to autoimmune skin disorders such as Alopecia Areata.
Mohammadreza Pakyari– Harvard University