Journal of Neuroscience, Vol 14, 1309-1319, Copyright © 1994 by Society for Neuroscience
The functional characteristics of Schwann cells cultured from human peripheral nerve after transplantation into a gap within the rat sciatic nerve
AD Levi, V Guenard, P Aebischer and RP Bunge
Miami Project to Cure Paralysis, University of Miami School of Medicine, Florida 33136.
The use of human Schwann cells (SCs) in transplantation to promote
regeneration in central and peripheral neural tissues must be preceded by
efforts to define the factors that regulate their functional expression.
Adult-derived human SCs can be isolated and purified in culture, but the
culture conditions that allow their full differentiation have not yet been
defined. We tested the functional capacity of these cells to enhance axonal
regeneration and myelinate regenerating axons in vivo by transplanting them
into the damaged PNS of an immune-deficient rat. SCs were purified from
human peripheral nerve obtained from organ donors. Semi-permeable guidance
channels were filled with a 30% Matrigel containing solution with or
without human SCs suspended at a density of 80 x 10(6) cells/ml. Channels
were implanted within an 8 mm gap of the transfected sciatic nerve of nude
female rats for a period of 4 weeks. Survival of the transplanted human SCs
was established by dissociating nerve explants taken from the regenerated
cable (after first placing them in culture for 5 d) and staining individual
cells for a primate-specific NGF receptor (PNGFr) and S 100. Only one-half
of the S 100-positive cells stained for the PNGFr, which indicated that the
regenerated cable contained an approximately equal number of human and rat
(host) SCs. The presence of some human myelin segments was confirmed by
immune staining with an HNK- 1 antibody that specifically labels human but
not rat myelin. The majority of the myelin segments in the regenerated
cable, however, were produced by the rat SCs. The number of myelinated
axons and the cross- sectional area of the cable were significantly greater
in channels seeded with human SCs when compared to channels containing the
diluted Matrigel solution alone. We conclude that purified cultured human
SCs can survive and substantially enhance axonal regeneration when
transplanted into the injured PNS of an immune-deficient rat. Some of the
transplanted human SCs are capable of myelinating regenerating rat axons
but are less successful than the host SCs.