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Transplantation of olfactory ensheathing cells fails to promote significant axonal regeneration from dorsal roots into the rat cervical cord

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Journal of Neurocytology

Abstract

The olfactory ensheathing cell (OEC) is a class of glial cell that has been reported to support regeneration in the central nervous system after various types of lesions, including rhizotomy of spinal dorsal roots at thoracic, lumbar and sacral levels. We have therefore carried out a detailed anatomical analysis to assess the efficacy of dorsal horn OEC transplants at promoting regeneration of primary afferents across the dorsal root entry zone (DREZ) at the cervical level in the adult rat. OECs were cultured from adult rat olfactory bulb and immunopurified (90% purity). Regeneration by large diameter afferents and by both peptidergic and non-peptidergic small diameter afferents was assessed using respectively cholera toxin B (CTB) labelling and immunocytochemistry for calcitonin gene-related peptide (CGRP) and the purinoceptor P2X3. Following an extensive (C3-T3) rhizotomy, CGRP and P2X3 immunoreactive axons regenerated across the rhizotomy site as far as the DREZ but there was no evidence of regeneration across the DREZ, except through sites where the OEC transplant was directly grafted into the DREZ. No evidence of regeneration into the dorsal horn by CTB-labelled axons was obtained. In addition, there was little sign of sprouting by intact axons in the vicinity of OEC transplant sites. In contrast to these results in vivo, cocultures of OECs and adult dorsal root ganglion cells showed that OECs stimulate extensive neurite outgrowth. The failure of the OECs to promote regeneration in vivo following cervical rhizotomy is therefore most likely due to factors in the environment of the graft site and/or the method of transplantation.

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Authors and Affiliations

  1. Instituto de Neurobiología Ramón y Cajal, Avenida Doctor Arce 37, 28002, Madrid, Spain

    Vilma Muñetón Goméz, Sara Caballero Chacón & Manuel Nieto-Sampedro

  2. Department of Neuroscience, Queen Mary University of London, Mile End Road, London, E1 4NS

    Sharon Averill, Von King, Qin Yang, Rachael Ward & John Priestley

  3. Unidad de Neurología Experimental, Hospital Nacional de Parapléjicos, Finca “La Peraleda” s/n, 45071, Toledo, Spain

    Ernesto Doncel Pérez & Julian Taylor

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  1. Vilma Muñetón Goméz
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  2. Sharon Averill
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  3. Von King
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Goméz, V.M., Averill, S., King, V. et al. Transplantation of olfactory ensheathing cells fails to promote significant axonal regeneration from dorsal roots into the rat cervical cord. J Neurocytol 32, 53–70 (2003). https://doi.org/10.1023/A:1027328331832

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