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

Katherine B. Santosa, Nithya J. Jesuraj, Andreu Viader, Matthew Macewan, Piyaraj Newton, Daniel A. Hunter, Susan E. Mackinnon, Philip J. Johnson

Research output: Contribution to journalArticle

40 Scopus citations

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.

Original languageEnglish
Pages (from-to)213-223
Number of pages11
JournalMuscle and Nerve
Volume47
Issue number2
DOIs
StatePublished - Feb 1 2013

Keywords

  • GDNF
  • Lentiviral vector
  • Nerve regeneration
  • Neurotrophic factor
  • Peripheral nerve injury
  • Schwann cells

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