Introduction: Clinical application of nerve allotransplantation has avoided limb amputation in human subjects and proven effective in restoring function. However, due to the morbidity associated with nonspecific immunosuppression, this approach has been limited to patients with unusually severe peripheral nerve injuries. Development of less morbid anti-rejection therapies would broaden the indications for nerve allotransplantation.

Methods: Eight haplotyped miniature swine were enrolled in the study. Ulnar nerve allografts were harvested from donor animals and cold preserved at 4º Celsius in University of Wisconsin solution. At time of donor nerve harvest, experimental animals underwent systemic portal venous infusion of UV-B irradiated donor antigen under fluoroscopic guidance. At 1 week after portal infusion, 5 cm cold preserved nerve allografts were injected with isogeneic Schwann cells or saline and microsurgically transplanted into an ulnar nerve defect.  Serial mixed lymphocyte reaction assays tracked changes in immunoreactivity over time, and grafted nerves were harvested at 20 weeks. 

Results: Histomorphometry showed marked enhancement in nerve regeneration across allografts injected with Schwann cells but no effect of donor portal infusion of UV-B donor antigen (see table below), although suppression of recipient alloimmune response was observed with donor antigen in immunologic assays. Mean fiber counts were 9194 ± 406 in nerves injected with Schwann cells versus 3924 ± 932 in nerves injected with saline (p<0.05), and percent nerve was 6.4 ± 3.0with Schwann cells versus 2.6 ± .53 with saline (p<0.05).

Conclusion: Schwann cell injection significantly enhances nerve regeneration across cold preserved peripheral nerve allografts.

 

Schwann Cells	Donor Antigen	Fiber Count	Percent Nerve	Fiber Width	Nerve Density	Fiber Areas	Percent Debris
Yes	No	13569	9.64	2.74	10527	4813	0.63
Yes	Yes	9974	7.80	3.72	5013	3890	0.92
Yes	Yes	9489	5.48	3.12	5273	2732	2.21
Yes	Yes	3749	2.66	2.75	2927	1326	3.50
No	No	4790	3.07	2.73	3429	1533	0.72
No	Yes	3605	1.91	2.59	2506	954	2.34
No	Yes	2755	2.44	2.96	2607	1217	1.03
No	Yes	4549	2.96	2.88	3108	1475	1.06