Cell therapy for spinal cord injury with olfactory ensheathing glia cells (OECs)

Abstract

The prospects of achieving regeneration in the central nervous system (CNS) have changed, as most recent findings indicate that several species, including humans, can produce neurons in adulthood. Studies targeting this property may be considered as potential therapeutic strategies to respond to injury or the effects of demyelinating diseases in the CNS. While CNS trauma may interrupt the axonal tracts that connect neurons with their targets, some neurons remain alive, as seen in optic nerve and spinal cord (SC) injuries (SCIs). The devastating consequences of SCIs are due to the immediate and significant disruption of the ascending and descending spinal pathways, which result in varying degrees of motor and sensory impairment. Recent therapeutic studies for SCI have focused on cell transplantation in animal models, using cells capable of inducing axon regeneration like Schwann cells (SchCs), astrocytes, genetically modified fibroblasts and olfactory ensheathing glia cells (OECs). Nevertheless, and despite the improvements in such cell-based therapeutic strategies, there is still little information regarding the mechanisms underlying the success of transplantation and regarding any secondary effects. Therefore, further studies are needed to clarify these issues. In this review, we highlight the properties of OECs that make them suitable to achieve neuroplasticity/neuroregeneration in SCI. OECs can interact with the glial scar, stimulate angiogenesis, axon outgrowth and remyelination, improving functional outcomes following lesion. Furthermore, we present evidence of the utility of cell therapy with OECs to treat SCI, both from animal models and clinical studies performed on SCI patients, providing promising results for future treatments.

Olfactory ensheathing cells from the nasal mucosa and olfactory bulb have distinct membrane properties

“…These may be a consequence of the discrepancies in the experiments and methods of assessment. The site of origin, the composition of cultures, and their proliferative state may also be crucial factors that determine success following transplantation, and these have been reviewed recently elsewhere (Assinck et al, ; Gladwin & Choi, ; Gomez et al, ). The regenerative capacity of OECs may be determined by the length of time that they are cultured prior to transplantation.…”

“…The life span of OSNs is relatively short, around 30 days in young mammals (Brann & Firestein, ), and so there is a need for continual neurogenesis in order to maintain a normal sense of smell. Harnessing the unusual neuroregenerative abilities of the olfactory system continues to be promoted as a therapeutic approach to the reversal of spinal cord injury and certain demyelinating conditions (Assinck, Duncan, Hilton, Plemel, & Tetzlaff, ; Ekberg & St John, ; Gladwin & Choi, ; Gomez et al, ; Yao et al, ). The olfactory mucosa (OM) represents a particularly attractive target for sourcing OECs for clinical transplantation, as it permits relatively noninvasive endoscopic harvesting from affected patients, healthy volunteers, or cadaveric specimens (Andrews, Poirrier, Lund, & Choi, ; Choi & Gladwin, ).…”

“…In addition, several lines of evidence suggest OECs derived from the OM may be especially beneficial for transplantation therapies (Yao et al, 2018). The physiological functions of peripheral OECs remain poorly understood at a cellular and molecular level (Chen, Kachramanoglou, Li, Andrews, & Choi, 2014;Gomez et al, 2018), and so it is currently unclear why this subtype of OECs could more successfully encourage neuronal regeneration. Much of our current understanding of neuroglial interactions comes from structural, molecular, and functional studies of rodent OECs, from either the OM or OB (Guerout et al, 2010;Hayat, Wigley, & Robbins, 2003;Higashi et al, 2001;Piantanida et al, 2019;Rash et al, 2005;Rela, Bordey, & Greer, 2010;Rela, Piantanida, Bordey, & Greer, 2015;Rieger, Deitmer, & Lohr, 2007).…”

Melatonin improves functional recovery in female rats after acute spinal cord injury by modulating polarization of spinal microglial/macrophages

“…To date, no effective therapy has been developed for this condition (Goldshmit et al, ). The pathogenesis of traumatic SCI broadly comprises two stages: primary injury refers to direct or indirect effects of trauma to the spinal cord, whereas the secondary injury involves complex etiologies, including hemorrhage, ischemia, hypoxia, inflammation, and edema (Ahuja & Fehlings, ; Gomez et al, ). Neuronal apoptosis is an important obstacle to restoring neurologic functions after SCI (Dou, Chen, Ran, & Jiang, ).…”

A Perfused Microfluidic System to Study the Differentiation of Neural Stem Cells in vitro

“…Injury to the central nervous system, mainly the neurons in the brain, is a common cause of nerve function loss that often leads to severe disabilities, such as Alzheimer disease [Hullmann et al, 2017;Patnaik et al, 2018], amyotrophic lateral sclerosis, and idiopathic Parkinson's disease [Sorce et al, 2017;Zanforlin et al, 2017]. Developing in vitro systems that can efficiently control the differentiation of neural stem cells into functional neurons represents one of the promising approaches to create opportunities in repairing the brain injury site [Liu et al, 2017;Nuryyev et al, 2017;Gómez et al, 2018].…”