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Journal of Neuroscience, Vol 12, 3310-3320, Copyright © 1992 by Society for Neuroscience
Syngeneic Schwann cells derived from adult nerves seeded in semipermeable guidance channels enhance peripheral nerve regeneration
V Guenard, N Kleitman, TK Morrissey, RP Bunge and P Aebischer
Section for Artificial Organs, Biomaterials and Cellular Technology, Brown University, Providence Rhode Island 02912.
At present, clinical strategies to repair injured peripheral nerve
concentrate on efforts to attain primary suture of the cut nerve ends. If
this is not possible, autografts are used to unite the separated nerve
segments. Both strategies are based on the recognition that the Schwann
cells resident in the peripheral nerve trunk play a crucial role in the
regenerative process. Neither strategy may be feasible, however, in
extensive or multiple injuries because the amount of autograft material is
limited, and allografts are subject to immune rejection. Artificially
produced nerve bridges constructed of autologous Schwann cells seeded in
guidance channels could be used to overcome these limitations. In the
present experiments, the potential of Schwann cells derived from adult
nerves and seeded in permselective guidance channels to promote neurite
regeneration across an 8 mm nerve gap was evaluated in transected rat
sciatic nerves. Immunological sequalae were evaluated by comparing Schwann
cells from syngeneic and heterologous rat strains. Schwann cells from
either adult outbred (Sprague-Dawley, CD) rats or inbred (Fisher, F) rats
were suspended in a Matrigel solution at a density of 80 x 10(6) cells/ml
(CD) or 40, 80, or 120 x 10(6) cells/ml (F-40, F-80, and F-120 channels,
respectively). Channels containing Schwann cells were compared to sciatic
nerve autografts, empty channels, or channels filled with Matrigel alone.
One day after seeding permselective synthetic guidance channels with a
Schwann cell suspension, a central cable of Schwann cells oriented along
the axis of the tube was formed due to syneresis of the hydrogel. By 3
weeks postimplantation, regenerating axons had grown into all channels and
autografts. Sciatic nerve autografts supported extensive regeneration,
containing 4-5 x 10(4) myelinated axons at the graft midpoint. The ability
of channels containing syngeneic Schwann cells to foster regeneration was
dependent on the Schwann cell seeding density. At the channel's midpoint,
the myelinated axon population in F-120 tubes was intermediate between that
in sciatic nerve autografts and F- 80 channels, and was significantly
higher than in F-40 or control channels. The nerve cable in Schwann
cell-containing tubes consisted of larger, more organotypic fascicles than
acellular control channels. In contrast, heterologous (CD) Schwann cells
elicited a strong immune reaction that impeded nerve regeneration. The
present study shows that cultured adult syngeneic Schwann cells seeded in
permselective synthetic guidance channels support extensive peripheral
nerve regeneration.(ABSTRACT TRUNCATED AT 400 WORDS)
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