Intra-graft injection of tacrolimus promotes survival of vascularized composite allotransplantation

Topical tacrolimus and steroids modulate T cells in acute rejection of hand allotransplantation: Two case reports

“…In vivo, tacrolimus has been shown to modulate Treg activity by modifying the expression levels of Foxp3‐regulated T‐cell receptor signal related‐genes (Kogina et al, ). Intragraft injection of tacrolimus may be another way to prolong VCA survival, but it is a relatively invasive treatment (Olariu et al, ). Combining immunosuppressants and steroidal anti‐inflammatory agents has also been shown to be an option to produce synergistic effects (Hewitt & Black, ).…”

Composite tissue allotransplantation: opportunities and challenges

“…100 Topical application of immunosuppression drugs with reduced systemic side effects has been applied successfully in face and upper limb transplantation. 101 Lower-grade rejections (Banff grades 1-2) have been successfully treated with topical tacrolimus and clobetasol. 102 Interestingly, preclinical studies have shown superior effects of topical compared to systemic immunosuppression in some cases.…”

“…102 Interestingly, preclinical studies have shown superior effects of topical compared to systemic immunosuppression in some cases. 101 A dichotomous response upon topical tacrolimus treatment has been observed in rats receiving hindlimb transplants; half of the animals rejected the graft after 70 days, Composite tissue allotransplantation: opportunities and challenges J Iske et al similar to untreated controls, while the other half did not show any signs of graft rejection 200 days post transplantation and had significantly lower pathological injury once assessed. 101 Topical high-dose application has not been linked to augmented systemic side effects, 101 encouraging VCA-specific immunosuppression.…”

Novel targeted drug delivery systems to minimize systemic immunosuppression in vascularized composite allotransplantation

“…Recently, our group reported that an intra-graft injection of high-dose tacrolimus may induce longterm survival with half of the treatment group of rats reaching 200 days' survival without signs of rejection [69]. Intra-graft tacrolimus application immediately after transplantation increased tissue drug availability, promoting the establishment of transient donor-cell chimerism and thus long-term graft acceptance.…”