Classical animal models for allogeneic limb transplantation have been based on rat and pig donor and recipients. This is due to a multiplicity of factors, including availability of animals, protocols for animal use, cost, vessel size, and husbandry factors. Mice however, offer an optimal model in that they have been carefully bred for strains that possess certain immunologic traits. Murine models of hindlimb transplantation, however, are technically very demanding and require skill and precision not necessary when performing transplants in larger animals. The authors devised this study to examine the effects of animal age on the success of anastomotic patency and graft survival, morbidity, and mortality in a mouse hindlimb allogeneic transplantation model. Balb/c strain mice received the hindlimb of C57B1/6 mice via femoral artery and vein anastomosis in a groin pocket, with an exposed skin paddle for clinical monitoring of ischemia and rejection. Group 1 (n=8) consisted of 2-3 month old mice weighing 17-20 grams. Group 2 (n=7) consisted of 7-8 month old mice weighing 24-27 grams. The skin paddles on the transplanted limbs were examined daily and transplant recipients who survived the operation with a viable transplant were sacrificed at the earliest signs of rejection. Histology and mixed lymphocyte culture were performed to verify rejection in sacrificed specimens.
The results of this study clearly favored younger mice as subjects for hind limb transplantation. In all parameters measured, results were better in the younger mice. Six of eight allografts in the juvenile mice survived and were eventually rejected (75% success). Only one of seven allografts in the older mice survived to rejection (14% success). The six failures in the older group were the result of early postoperative complications and very early allograft loss prior to the onset of rejection. The observable ischemia in the older group was also more severe and at a higher anatomic level in the few animals that survived the procedure than in the surviving juvenile animals. Both the higher success rate and the lower morbidity in the juvenile animals were statistically significant. The reasons for the higher success in the young mice remains speculative. Vascular developmental changes, maturation of the coagulation system and decreased collateral vessel formation in older mice were all possible theories put forth. It appears that in the technically demanding murine limb transplantation model, juvenile mice offer a better chance of successful limb transplantation than older mice.
Journal of Reconstructive Microsurgery