Biology Reference
In-Depth Information
growth (
Chen, Yu, & Strickland, 2007
). Moreover, denervated
Schwann cells overexpress fibronectin, laminin, tenascin, and some
proteoglycans, which create a substrate for axonal elongation. The phe-
notype of reactive Schwann cells resembles the one of immature
Schwann cells, and they form a permissive substrate for regeneration.
When these cells regain contact with the axons, they redifferentiate
again (
Jessen & Mirsky, 2008
).
Wallerian degeneration represents the basis for the nerve regeneration and
target reinnervation processes (
Battiston, Geuna, Ferrero, & Tos, 2005;
Schmidt & Leach, 2003; Terzis, Sun, & Thanos, 1997
). In severe injuries,
nerve regeneration begins only after Wallerian degeneration has run its
course, but in mild injuries, the regenerative and repair processes begin
almost immediately. The rate of axonal regrowth is determined by changes
within the cell body, the activity of the specialized growth cone at the tip of
each axon sprout, and the resistance of the injured tissue between cell body
and end organ.
Regenerating axons are usually produced at the node of Ranvier located
close to the proximal stump of the lesion (
Hopkins & Slack, 1981;
McQuarrie, 1985
). Nodal sprouts usually contain vesicles of various sizes,
and as the sprouts develop into well-formed growth cones, the number
of vesicles markedly increases. Sprouts from the node of Ranvier extend
through their own basal lamina tubes in the proximal segment, traverse
the narrow gap of connective tissue between the proximal and distal stumps,
and finally enter the distal nerve segment.
During extension through the Schwann cell column, regenerating axons
grow along the Schwann cell basal lamina. Axon-Schwann cell attachment
is mediated by various adhesion molecules including the immunoglobulin
superfamily, for example, neural cell adhesion molecule (N-CAM) and
L1, and the cadherin superfamily, for example, N-cadherin and
E-cadherin, whereas axon basal lamina contact is for the most part mediated
by laminin (
Letourneau, Condic, & Snow, 1994
). These adhesion molecules
are no longer detected when Schwann cells begin to form the myelin sheath
around the axon, whereas the mature unmyelinated fibers continue to
exhibit such adhesion molecules (
Ide, 1996
).
When surgical repair of the nerve is required, the goal is to guide reg-
enerating sensory, motor, and autonomic axons to the distal nerve segment
to maximize the chance of target reinnervation (
Pfister et al., 2011
). Nerve
reconstruction by tissue engineering has seen an increasing interest over the
past years (
Leach & Schmidt, 2005; Pfister et al., 2011
). Despite the
