Nerve allografts supplemented with schwann cells overexpressing glial-cell-line-derived neurotrophic factor

Muscle Nerve. 2013 Feb;47(2):213-23. doi: 10.1002/mus.23490. Epub 2012 Nov 21.

Abstract

Introduction: We sought to determine whether supplementation of acellular nerve allografts (ANAs) with Schwann cells overexpressing GDNF (G-SCs) would enhance functional recovery after peripheral nerve injury.

Methods: SCs expanded in vitro were infected with a lentiviral vector to induce GDNF overexpression. Wild-type SCs (WT-SCs) and G-SCs were seeded into ANAs used to repair a 14-mm nerve gap defect. Animals were harvested after 6 and 12 weeks for histomorphometric and muscle force analysis.

Results: At 6 weeks, histomorphometry revealed that ANAs supplemented with G-SCs promoted similar regeneration compared with isograft at midgraft. However, G-SCs failed to promote regeneration into the distal stump. At 12 weeks, ANAs with G-SCs had lower maximum and specific force production compared with controls.

Conclusions: The combined results suggest that consistent overexpression of GDNF by G-SCs trapped axons in the graft and prevented functional regeneration.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Glial Cell Line-Derived Neurotrophic Factor / metabolism*
  • Male
  • Nerve Regeneration / physiology
  • Nerve Tissue / metabolism
  • Nerve Tissue / transplantation*
  • Peripheral Nerve Injuries / metabolism
  • Peripheral Nerve Injuries / surgery*
  • Rats
  • Rats, Inbred Lew
  • Rats, Sprague-Dawley
  • Recovery of Function / physiology*
  • Schwann Cells / metabolism
  • Schwann Cells / transplantation*

Substances

  • Glial Cell Line-Derived Neurotrophic Factor