GalT Knockout Porcine Nerve Xenografts Support Axonal Regeneration in a Rodent Sciatic Nerve Model.

Abstract

Background: Nerve xenografts harvested from transgenic α1,3-galactosyltransferase knockout pigs lack the epitope responsible for hyperacute rejection in pig-to-primate transplants. It is unknown whether these cold-preserved nerve grafts support axonal regeneration in another species during and after immunosuppression. The authors compared outcomes between autografts and cold-preserved xenografts in a rat sciatic model of nerve gap repair.

Methods: Fifty male Lewis rats had a 1-cm sciatic nerve defect repaired using autograft and suture ( n = 10); 1-week or 4-week cold-preserved xenograft and suture ( n = 10 per group); or 1-week or 4-week cold-preserved xenograft and photochemical tissue bonding using a human amnion wrap ( n = 10 per group). Rats with xenografts were given tacrolimus until 4 months postoperatively. At 4 and 7 months, rats were killed and nerve sections were harvested. Monthly sciatic functional index (SFI) scores were calculated.

Results: All groups showed increases in SFI scores by 4 and 7 months. The autograft suture group had the highest axon density at 4 and 7 months. The largest decrease in axon density from 4 to 7 months was in the group with 1-week cold-preserved photochemical tissue bonding using a human amnion wrap. The only significant difference between group SFI scores occurred at 5 months, when both 1-week cold-preserved groups had significantly lower scores than the 4-week cold-preserved suture group.

Conclusions: The results suggest that α1,3-galactosyltransferase knockout nerve xenografts may be viable alternatives to autografts. Further studies of long-gap repair and comparison with acellular nerve allografts are needed.

Clinical relevance statement: This proof-of-concept study in the rat sciatic model demonstrates that cold-preserved α1,3-galactosyltransferase knockout porcine xenografts support axonal regeneration and viability following immunosuppression withdrawal. These results further suggest a role for both cold preservation and photochemical tissue bonding in modulating the immunological response at the nerve repair site.