Abstract

Adipose-derived stem cells were isolated from rats and differentiated to a Schwann cell-like phenotype in vitro. The differentiated cells (dADSCs) underwent self-alignment in a tethered type-1 collagen gel, followed by stabilisation to generate engineered neural tissue (EngNT-dADSC). The pro-regenerative phenotype of dADSCs was enhanced by this process, and the columns of aligned dADSCs in the aligned collagen matrix supported and guided neurite extension in vitro. EngNT-dADSC sheets were rolled to form peripheral nerve repair constructs that were implanted within NeuraWrap conduits to bridge a 15 mm gap in rat sciatic nerve. After 8 weeks regeneration was assessed using immunofluorescence imaging and transmission electron microscopy and compared to empty conduit and nerve graft controls. The proportion of axons detected in the distal stump was 3.5 fold greater in constructs containing EngNT-dADSC than empty tube controls. Our novel combination of technologies that can organise autologous therapeutic cells within an artificial tissue construct provides a promising new cellular biomaterial for peripheral nerve repair.

Highlights

  • Peripheral nerve injuries lead to pain and significant disability in many affected individuals

  • Rat adipose-derived stem cells were differentiated to a Schwann cell-like phenotype as previously described [19]

  • Our results show that the EngNT-dADSC can be used to form an effective peripheral nerve repair device to bridge a critical sized nerve gap

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Summary

Introduction

Peripheral nerve injuries lead to pain and significant disability in many affected individuals. Each year approximately 300,000 people of working age in Europe experience a peripheral nerve injury (PNI) [1]; of these less than 50% regain full function after treatment [2,3]. For peripheral nerve damage that results in gaps greater than approximately 3 cm, the current clinical gold standard treatment is the nerve autograft. Results have shown that guidance conduit structures and living cells are essential for the repair of larger nerve gaps to provide trophic support and recreate the environment provided by the nerve autograft [4e9]. Schwann cell-like cells derived from stem cells are a more attractive source because they can potentially be obtained from the patient for use in an autologous therapy [13]. Autologous cells are generally considered to be more readily accepted by the patient because they do not provoke an immune reaction [7,14]

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