Chronic Spinal Injury Repair by Olfactory Bulb Ensheathing Glia and Feasibility for Autologous Therapy

Abstract

Olfactory bulb ensheathing glia (OB-OEG) promote repair of spinal cord injury (SCI) in rats after transplantation at acute or subacute (up to 45 days) stages. The most relevant clinical scenario in humans, however, is chronic SCI, in which no more major cellular or molecular changes occur at the injury site; this occurs after the third month in rodents. Whether adult OB-OEG grafts promote repair of severe chronic SCI has not been previously addressed. Rats with complete SCI that were transplanted with OB-OEG 4 months after injury exhibited progressive improvement in motor function and axonal regeneration from different brainstem nuclei across and beyond the SCI site. A positive correlation between motor outcome and axonal regeneration suggested a role for brainstem neurons in the recovery. Functional and histological outcomes did not differ at subacute or chronic stages. Thus, autologous transplantation is a feasible approach as there is time for patient stabilization and OEG preparation in human chronic SCI; the healing effects of OB-OEG on established injuries may offer new therapeutic opportunities for chronic SCI patients.

Axon Regeneration Can Facilitate or Suppress Hindlimb Function after Olfactory Ensheathing Glia Transplantation

“…After a complete spinal cord transection, however, achieving axon regeneration across the lesion that contributes to functional recovery remains a difficult challenge. Olfactory ensheathing glia (OEG) transplantation reportedly promotes tissue sparing, axon remyelination, and improvements in motor performance in incomplete and complete adult spinal cord injury (SCI) models (Imaizumi et al, 1998; Ramón-Cueto et al, 2000; García-Alías et al, 2003; Li et al, 2003; Fouad et al, 2005; Li et al, 2007; Kubasak et al, 2008; Muñoz-Quiles et al, 2009). However, the results of SCI studies involving OEG transplantation vary substantially depending on the injury model, the duration of the study, and the source, age, and methods used to prepare and transplant the OEG (Franssen et al, 2007).…”

Transplantation of Olfactory Ensheathing Cells in Spinal Cord Injury

“…Indeed, acute transplantation of OECs has shown higher functional and anatomical outcomes compared to delayed transplant (Lopez-Vales et al 2006). However, other studies have not detected significant differences in outcomes for acute versus delayed trans-plantation of OECs (Munoz-Quiles et al 2009;Centenaro et al 2011;Torres-Espin et al 2014). Despite this, it would seem reasonable that differences in efficacy and outcomes of acute versus delayed treatment may be revealed if improvements in the experimental conditions were made and the purity of the cell preparations and co-transplanted cells was optimized (as discussed below).…”

Adult Stem Cell Transplants for Spinal Cord Injury Repair: Current State in Preclinical Research

“…[192] rat OECs enhance axonal regeneration and improve functional recovery in a chronic SCI model. [221] rat hOECS improve functional recovery in a contusion SCI model and promote tissue sparing. [214] the use of NSCs, including inefficient tracking systems and moderate cell survival after transplantation [106].…”

“…Long-distance axonal regeneration toward sublesional segments was reported in OEC-grafted rats [211,219], associated to limited but significant improvement in locomotion behavior and restitution of motor evoked potentials in some cases. The effects of transplanted OECs are more obvious after acute than delayed transplantation, although two recent reports have described that chronic transplants are still efficient to enhance recovery of the SCI [220,221]. The combination of OECs with SCs was previously tested, and may be an approach to promote restitution of the disrupted spinal pathways [191,192].…”