Abstract
BackgroundBased on growing evidence that some adult multipotent cells necessary for tissue regeneration reside in the walls of blood vessels and the clinical success of vein wrapping for functional repair of nerve damage, we hypothesized that the repair of nerves via vein wrapping is mediated by cells migrating from the implanted venous grafts into the nerve bundle.Methodology/Principal FindingsTo test the hypothesis, severed femoral nerves of rats were grafted with venous grafts from animals of the opposite sex. Nerve regeneration was impaired when decellularized or irradiated venous grafts were used in comparison to untreated grafts, supporting the involvement of venous graft-derived cells in peripheral nerve repair. Donor cells bearing Y chromosomes integrated into the area of the host injured nerve and participated in remyelination and nerve regeneration. The regenerated nerve exhibited proper axonal myelination, and expressed neuronal and glial cell markers.Conclusions/SignificanceThese novel findings identify the mechanism by which vein wrapping promotes nerve regeneration.
Highlights
Wrapping the scarred nerves with autogenous vein grafts has been used effectively for the treatment of peripheral neuropathy in both experimental and clinical settings [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17]
Adipose vasculature has been identified as a niche where white fat progenitor cells reside [22], and our publications describe a perivascular origin for multipotent myoendothelial cells and pericytes in human skeletal muscle [23], [24]
To explore our hypothesis that the healing of peripheral nerves is mediated by vascular cells from the venous grafts, we examined the migration of the cells derived from vascular walls in nerve repair by altering the venous grafts prior to transplantation using decellularization and irradiation methods
Summary
Wrapping the scarred nerves with autogenous vein grafts has been used effectively for the treatment of peripheral neuropathy in both experimental and clinical settings [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17]. Results of these studies have shown improvement of the nerve function and the symptoms associated with recurrent compressive peripheral neuropathy [5,6,7,8,9,10], [12], [13], [17], carpal tunnel syndrome [6], [14], tarsal tunnel syndrome [8], cubital tunnel syndrome [17], prevention of scar formation [4], [7], [11], and alleviation of painful neuroma [15], [16]. Based on growing evidence that some adult multipotent cells necessary for tissue regeneration reside in the walls of blood vessels and the clinical success of vein wrapping for functional repair of nerve damage, we hypothesized that the repair of nerves via vein wrapping is mediated by cells migrating from the implanted venous grafts into the nerve bundle
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