Original Articles
Molecular Therapy (2006) 13, 598–608; doi: 10.1016/j.ymthe.2005.11.014
A Clonal Cell Line from Immortalized Olfactory Ensheathing Glia Promotes Functional Recovery in the Injured Spinal Cord
M. Teresa Moreno–Flores1, Elizabeth J. Bradbury2, M. Jesús Martín-Bermejo1, Marta Agudo2, Filip Lim1, Érika Pastrana1, Jesús Ávila1, Javier Díaz-Nido1, Stephen B. McMahon2 and Francisco Wandosell1
- 1Centro de Biología Molecular "Severo Ochoa," Facultad de Ciencias, Universidad Autónoma de Madrid, 28049 Madrid, Spain
- 2Sensory Function Group, Centre for Neuroscience Research, Hodgkin Building, Kings College London, Guy's Campus, London Bridge SE1 1UL, UK
Correspondence: Francisco Wandosell, Fax: +34 91 3974799. E-mail: FWANDOSELL@cbm.uam.es
Received 19 April 2005; Revised 6 October 2005; Accepted 2 November 2005.
Abstract
Immortalized cell lines of olfactory ensheathing glia (OEG) that maintain the proregenerative properties of primary cultures provide an unlimited source of OEG for both basic and applied studies. Indeed, one specific immortalized rat OEG clonal line (TEG3) proved to be as good as primary OEG in promoting neuritogenesis and axon regeneration in culture models. Thus, we examined the capacity of TEG3 to promote axonal repair in an animal model of spinal cord injury, dorsal column crush. TEG3 cells can acquire astrocyte-like or Schwann cell-like morphology depending on the conditions under which they are cultured. In the injured spinal cord, prelabeled TEG3 survived for at least 10 weeks after grafting and they integrated into the spinal cord, adopting Schwann cell-like, astrocyte-like, or intermediate morphologies. In TEG3-transplanted animals, sensory projection axons grow into the lesion site and there was robust sprouting/axonal growth of the corticospinal tract, both into and beyond the lesion site, after crushing of the spinal cord–dorsal columns. TEG3-transplanted animals also recovered sensory and motor function in tape removal and beam walking behavioral tests. These data indicate that certain immortalized cell lines derived from a single cell can maintain the regenerative properties of primary OEG.
Keywords:
olfactory ensheathing glia, immortalized clonal line, spinal cord functional recovery, central nervous system repair
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