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Human Neural Stem Cells Used in Nerve Repair

Artificial tissues made from neural stem cells offer a promising approach for improving the treatment of severe peripheral nerve injuries.

ABSTRACT

An allogeneic ‘off the shelf’ therapeutic strategy for peripheral nerve tissue engineering using clinical grade human neural stem cells.

Sci Rep. 2018 Feb 13;8(1):2951. doi: 10.1038/s41598-018-20927-8.

O’Rourke C1,2, Day AGE1,2, Murray-Dunning C1, Thanabalasundaram L2,3, Cowan J4, Stevanato L3, Grace N5, Cameron G5, Drake RAL5, Sinden J2,3, Phillips JB6,7,8.

Author information

  1. Department of Biomaterials & Tissue Engineering, UCL Eastman Dental Institute, University College London, London, UK.
  2. UCL Centre for Nerve Engineering, London, UK.
  3. ReNeuron, Pencoed, Bridgend, Wales, UK.
  4. Royal National Orthopaedic Hospital, Stanmore, UK.
  5. Sartorius Stedim Biotech, Royston, UK.
  6. Department of Biomaterials & Tissue Engineering, UCL Eastman Dental Institute, University College London, London, UK. [email protected].
  7. UCL Centre for Nerve Engineering, London, UK. [email protected].
  8. Department of Pharmacology, UCL School of Pharmacy, University College London, London, UK. [email protected].

Artificial tissues constructed from therapeutic cells offer a promising approach for improving the treatment of severe peripheral nerve injuries. In this study the effectiveness of using CTX0E03, a conditionally immortalised human neural stem cell line, as a source of allogeneic cells for constructing living artificial nerve repair tissue was tested. CTX0E03 cells were differentiated then combined with collagen to form engineered neural tissue (EngNT-CTX), stable aligned sheets of cellular hydrogel. EngNT-CTX sheets were delivered within collagen tubes to repair a 12 mm sciatic nerve injury model in athymic nude rats. Autologous nerve grafts (autografts) and empty tubes were used for comparison. After 8 weeks functional repair was assessed using electrophysiology. Further, detailed histological and electron microscopic analysis of the repaired nerves was performed. Results indicated that EngNT-CTX supported growth of neurites and vasculature through the injury site and facilitated reinnervation of the target muscle. These findings indicate for the first time that a clinically validated allogeneic neural stem cell line can be used to construct EngNT. This provides a potential ‘off the shelf’ tissue engineering solution for the treatment of nerve injury, overcoming the limitations associated with nerve autografts or the reliance on autologous cells for populating repair constructs.

PMID: 29440680 PMCID: PMC5811594 DOI: 10.1038/s41598-018-20927-8