A novel model for chronic rejection in vascularized composite allotransplantation identifies CXCL9-11 as potential biomarkers

Global mRNA expression profiling of transplanted rat hindlimbs (muscle and skin) were collected using Agilent rat whole genome array (Agilent-028282 Whole Rat Genome Microarray 4x44K v3). Hind limb transplantation between Fischer344 (donor) and Lewis (recipient) rats were performed. Isogenic transplantations served as controls. Administration of irregular immunosuppression induced chronic rejection. At the endpoint (post-operativ day 100), hind limbs presented clinicial, histomorphological and genetic changes, known to be highly suspicious for chronic rejection. Each group consisted of n=5 animals. Isogenic hind limb transplantations (Lewis as donor and recipient) served as controls and did not receive any immunosuppression. The chronic rejection group was treated only when signs of an acute skin rejection e.g. erythema or edema (defined as foot-swelling of ≥ 25 %) occured. Both muscle and skin of each group are represented by two biological replicates.