Bridging Schwann cell transplants promote axonal regeneration from both the rostral and caudal stumps of transected adult rat spinal cord.
Transplantation of cellular components of the permissive peripheral nerve environment in some types of spinal cord injury holds great promise to support regrowth of axons through the site of injury. In the present study, Schwann cell grafts were positioned between transected stumps of adult rat thoracic spinal cord to test their efficacy to serve as bridges for axonal regeneration. Schwann cells were purified in culture from adult rat sciatic nerve, suspended in Matrigel: DMEM (30:70), and drawn into polymeric guidance channels 8 mm long at a density of 120 x 10(6) cells ml-1. Adult Fischer rat spinal cords were transected at the T8 cord level and the next caudal segment was removed. Each cut stump was inserted 1 mm into the channel. One month later, a bridge between the severed stumps had been formed, as determined by the gross and histological appearance and the ingrowth of propriospinal axons from both stumps. Propriospinal neurons (mean, 1064 +/- 145 SEM) situated as far away as levels C3 and S4 were labelled by retrograde tracing with Fast Blue injected into the bridge. Near the bridge midpoint there was a mean of 1990 +/- 594 myelinated axons and eight times as many nonmyelinated, ensheathed axons. Essentially no myelinated or unmyelinated axons were observed in control Matrigel-only grafts. Brainstem neurons were not retrogradely labelled from the graft, consistent with growth of immunoreactive serotonergic and noradrenergic axons only a short distance into the rostral end of the graft, not far enough to reach the tracer placed at the graft midpoint. Anterograde tracing with PHA-L introduced rostral to the graft demonstrated that axons extended the length of the graft but essentially did not leave the graft. This study demonstrates that Schwann cell grafts serve as bridges that support (1) regrowth of both ascending and descending axons across a gap in the adult rat spinal cord and (2) limited regrowth of serotonergic and noradrenergic fibers from the rostral stump. Regrowth of monoaminergic fibres into grafts was not seen in an earlier study of similar grafts placed inside distally capped rather than open-ended channels. Additional intervention will be required to foster growth of the regenerated axons from the graft into the distal cord tissue.
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Chambers Family Electron Microscopy Laboratory, Miami Project to Cure Paralysis, FL, USA.
Chen
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Guénard
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Kleitman
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Bunge
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D000578:Amidines; D000818:Animals; D001370:Axonal Transport; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure; D017690:Cell Transplantation; D002478:Cells, Cultured; D005260:Female; D008854:Microscopy, Electron; D009413:Nerve Fibers, Myelinated / Q000502:physiology / Q000648:ultrastructure; D009416:Nerve Regeneration; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D010835:Phytohemagglutinins; D051381:Rats; D011916:Rats, Inbred F344; D012583:Schwann Cells / Q000166:cytology / Q000502:physiology* / Q000637:transplantation*; D012584:Sciatic Nerve / Q000166:cytology*; D013116:Spinal Cord / Q000502:physiology*; D018998:Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate
D000578:Amidines; D010835:Phytohemagglutinins; D018998:Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate; C031455:diamidino compound 253-50; C100156:leukoagglutinins, plants