Nerve regeneration in rat peripheral nerve allografts: An assessment of the role of endogenous neurotrophic factors in nerve cryopreservation and regeneration.

Abstract

Peripheral nerve injury is a common clinical problem that often leads to significant functional impairment or even complete paralysis. Allograft has been proposed as a potential repair strategy for peripheral nerve injuries. Furthermore, peripheral nerve cryopreservation may result in nearly unlimited supply of grafts. However, the concentration of neurotrophic factors secreted by Schwann cells (SCs) in the local micro-environment after transplantation may not be sufficient for the survival of neuronal soma and axonal regeneration. Here, we investigated the effect of endogenous neurotrophic factors (ENTFs) on nerve regeneration in rats after the allograft of a cryopreserved sciatic nerve. ENTFs were highly expressed in the sciatic nerves pretreated for 14 days. Although the number of surviving cells in the sciatic nerves and their immunogenicity were low in the 14-day group after 4weeks of cryopreservation, they continued to express high levels of ENTFs in vitro. At 1 week postoperation, the 14-day Allo group showed low plasma levels of interleukin-2, interferon-γ and tumour necrosis factor-alpha and low cellular immune response. At 20 weeks postoperation, nerve regeneration and functional recovery in the 14-day Allo group was similar to that in the fresh isograft group but better than that in the cryopreserved-fresh allograft and fresh allograft groups. Thus, ENTFs were induced in vitro after pretreatment of the sciatic nerve. Following cryopreservation, the sciatic nerves with high levels of ENTFs continued to express high levels of ENTFs in vitro. The immune response after allograft was weak, which promoted recipient nerve regeneration.