The ability of human Schwann cell grafts to promote regeneration in the transected nude rat spinal cord

Advances in the purification and expansion of Schwann cells (SCs) from adult human peripheral nerve, together with biomaterials development, have made the construction of unique grafts with defined properties possible. We have utilized PAN/PVC guidance channels to form solid human SC grafts which can be transplanted either with or without the channel. We studied the ability of grafts placed with and without channels to support regeneration ansi, to influence functional recovery; characteristics of the graft and host/graft interface wore also compared. The T9-T10 spinal cord of nude rats was resected and a graft was placed across the gap; methylprednisolone was delivered acutely to decrease secondary injury. Channels minimized the immigration of connective tissue into grafts but contributed to some necrotic tissue loss, especially in the distal spinal cord. Grafts without channels contained more myelinated axons ((x) over bar = 2129 +/- 785) vs ((x) over bar = 1442 +/- 514) and were larger in cross-sectional area ((x) over bar = 1.53 +/- 0.24 mm(2)) vs ((x) over bar = 0.95 +/- 0.86 mm(2)). The interfaces formed between the host spinal cord and the grafts placed without channels were highly interdigitated and resembled CNS-PNS transition zones; chondroitin sulfate proteoglycans was deposited there. Whereas several neuronal populations including propriospinal, sensory, motoneuronal, and brainstem neurons regenerated into human SC grafts, only propriospinal and sensory neurons were observed to reenter the host spinal cord. Using combinations of anterograde and retrograde tracers, we observed regeneration of propriospinal neurons up to 2.6 mm beyond grafts. We estimate that 1% of the fibers that enter grabs reenter the host spinal cord by 45 days after grafting. Following retrograde tracing from the distal spinal cord, more labeled neurons were unexpectedly found in the region of the dextran amine anterograde tracer injection site where a marked inflammatory reaction had occurred. Animals with bridging grafts obtained modestly higher scores during open field [((x) over bar = 8.2 +/- 0.35) vs ((x) over bar = 6.8 +/- 0.42), P = 0.02] and inclined plane testing (x) over bar = 38.6 +/- 0.542) vs ((x) over bar = 36.3 +/- 0.53), P = 0.006] than animals with similar grafts in distally capped channels, in summary, this study showed that in the nude rat given methylprednisolone in combination with human SC grafts, some regenerative growth occurred beyond the graft and a modest improvement in function was observed, (C) 1997 Academic Press.