Basic NeuroscienceAthymic rat model for studying acellular human allograft

- Optimizing “off the shelf” use of human acellular nerve allograft is limited by the lack of an animal model.
- We propose the use of an immunocompromised athymic rat to overcome previous xenograft rejection seen in cross-species grafts.
- Nerve regeneration following repair with xenograft was better tolerated in athymic rats than euthymic, immunocompetent rats.
- The use of an athymic rat model for studying human acellular allograft warrants further investigation.

BackgroundAlthough human acellular nerve allograft is a promising nerve repair tool, optimizing graft application and understanding effective graft dimensions has been hampered by lack of an appropriate animal model. Rodent nerve acellular allograft can be tested in the utilitarian rodent nerve repair model, but testing different size options is limited by the size of the rodent donor animal. Human acellular nerve allograft offers the variety of sizes desired for more complete study but poses a high risk of rejection as xenograft tissue in the rodent model. Athymic nude rats are less prone to reject xenograft tissue due to their immunocompromised state and may offer an animal model for testing human acellular allograft.MethodsFifteen athymic nude and 15 Sprague-Dawley rats underwent unilateral excision and repair of a 10 mm tibial nerve segment using 10 mm of human acellular nerve graft. Testing at 3 months consisted of muscle force measurements, wet muscle weight, and histological assessment from the middle of the nerve grafts.ResultsAthymic rats repaired with human acellular xenograft demonstrated higher reinnervated muscle weight Gross inspection of the xenograft in euthymic rats revealed a brown and scarred center and histological inspection demonstrated larger axon diameters, and higher midgraft axon counts in the grafts of athymic rats.Comparison with existing methods: The athymic rat has been used in many studies that require an immunocompromised host, including implantation of foreign nervous tissue. Previous attempts at implanting acellular nerve xenograft into immunocompetent rats have yielded suboptimal results when compared to allograft. This study is the first to test acellular human nerve allograft in an athymic rat.ConclusionThe nerve regeneration was better in human acellular nerve allograft implanted into immunocompromised athymic rats when compared to euthymic rats supporting a potential role of this model in studying acellular human nerve tissue.