Project: Research project

Project Details


It is well known that peripheral nerve constitutes a favorable
environment for supporting axonal regeneration. However, the precise
nature of cellular and non-cellular elements offering this support to the
regenerating axons remains to be defined. Peripheral nerve grafts have
been used to bridge long gaps in the injured peripheral nerve in
experimental and clinical situations. The disadvantages of using nerve
autograft (obtained from the same individual) is its limited availability
and inevitable loss of function at the autograft location. Hence, nerve
allografts obtained from other individuals have been utilized in nerve
repair. We recently reported that acellular basal lamina allografts,
lacking viable cells, exhibit reduced immunogenicity and were better
tolerated by the host in comparison to cellular allografts. The rate and
extent of axonal regeneration through acellular grafts was compromised
in comparison to cellular grafts. The experiments proposed here will
determine the role of Schwann cells and growth factor(s) on regeneration,
in order to enhance axonal regeneration through acellular grafts. The
hypothesis to be tested is that introduction of Schwann cell derivatives
(i.e., growth factors) into acellular nerve segments can enhance their
ability to support regeneration, and still maintain reduced
immunogenicity. The underlying cellular processes involved in
regeneration are also to be defined. Three independent strategies will
be employed to modify the acellular grafts to enhance their regeneration
supporting ability. These are: pretreatment of acellular nerves with
nerve growth factor and ciliary neurotrophic factor, two factors known
to influence neuronal survival and axonal growth; pretreatment of
acellular nerves with soluble extract(s) prepared from peripheral nerve;
and coculture of acellular nerves with Schwann cells. Inbred strains of
rats will be used to determine the immunologic fate of grafted nerves,
and to determine the extent of axonal regeneration through the various
grafts by morphological and physiological methods. These results will
define the role of specific growth factors and other treatments on the
regeneration process through acellular basal lamina grafts. The findings
may lead to the development of an ideal "bioprosthesis" for nerve gap
repair, allowing maximum recovery after nerve injury.
StatusNot started


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