Nerve regeneration through cryo-treated xenogeneic nerve grafts.

Abstract

Cryo-treated nerves whose Schwann cells had been killed by repeated freezing and thawing were xenogenically grafted into sciatic nerves from rats (Wistar, as donor) to mice (ddy strain, as recipient) to examine whether Schwann cell basal lamina tubes of cryo-treated xenogeneic grafts were effective conduits for regenerating axons. For comparison and evaluation of the effectiveness of this technique, experiments using grafts without the cryo-treatment were carried out. Cells in cryo-treated xenografts degraded into cell debris immediately after grafting and then were phagocytized by macrophages. After the cellular components had been removed from the graft, Schwann cell basal laminae remained intact in situ, serving as conduits for the regenerating axons. The process of nerve regeneration was almost the same as that observed in cryo-treated auto- and allografts, except that the regeneration was slightly delayed in the xenogeneic graft. In contrast, an extensive cell infiltration occurred in the non-treated grafts. It appeared that the donors Schwann cells in the graft deteriorated due to immunological reactions and were finally eliminated by macrophages, leaving their basal laminae undamaged in situ. The initiation of nerve regeneration including perineurial sheath formation in non-treated grafts was, therefore, significantly delayed, but once begun, it proceeded in the same manner as in the cryo-treated grafts. These findings strongly indicate that Schwann cell basal laminae can serve as effective pathways for regenerating axons even in the xenograft. Moreover, cryo-treated xenogeneic grafts are more desirable than non-treated ones, since dead Schwann cells in the former can be removed in the early period (4-14 days) from the graft without causing any immunological reaction, thus resulting in the facilitation of nerve regeneration.