Human nerve xenografting in nude mouse: experimental study of graft revascularization

In the nude mouse, the congenital absence of T lymphocytes makes it possible to implant human nerve grafts without rejection or iatrogenic modifications (by immunosuppression) of human and murine tissues. Medial antebrachial cutaneous nerves were harvested from human cadavers 1-18 hours after death. These nerve grafts were implanted using different techniques in nude mice. All the grafts were macroscopically and microscopically revascularized 3 days after implantation. The modifications in time of this vascularization could be studied with precision through the use of repeated biopsies. The absence of human blood group antigens on the neovessel endothelium suggested a murine origin for angiogenesis. In situ DNA hybridizations with human and mouse DNA confirmed this origin. The topography of the revascularization (maximal in the perineurium and endoneurium) and the almost complete absence of human cells other than Schwann cells in the grafts at the peak of angiogenesis (26 days after grafting) suggested that Schwann cells had a determining role in graft vascularization. The irradiation of the nerve grafts with a dose of 30 grays before implantation did not modify significantly their histologic appearance compared to the control group, whereas an irradiation of 60 grays led to massive lesions. The neurotization of murine axons led to chimerical structures of normal histologic appearance, with vascularization similar to that observed in nonneurotized nerves. Through chimerism (human Schwann cells, murine vessels and axons) this model makes it possible to dissociate the respective role of the host and of the nerve graft in angiogenesis and suggests the existence of growth factors produced by the human Schwann cells.