Regenerative Medicine Cluster Initiative in BC
A UBC Research Excellence Cluster

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Facial nerve regeneration using olfactory stem cells and hydrogels

Olfactory stem cells (OSCs) are neural stem cells found in the olfactory mucosa which have shown promising regenerative potential in spinal cord injury models by promoting axonal growth when engrafted into the injured area. Recently in a study published in Stem Cells Translational Medicine, a team from Nagoya University (Japan) set to investigate the regenerative potential of olfactory stem cells in facial nerve injury, one of the most common complications of temporal bone trauma. The research team obtained OSCs from dissected neonatal olfactory mucosa and cultured the isolated cells in ultra-low attachment plates, leading to the formation of olfactory spheres. These olfactory spheres not only showed positive immunoreactivity for neural stem cell markers (Nestin, Musashi-1), but also differentiation markers for astrocytes (Gfap), oligodendrocytes (GalC), and neurons (ßIII-tubulin), as well as demonstrating secretion of Gslectin-1, growth arrest-specific 1 (GAS1), insulin-like growth factor binding protein 2 and 3 (IGF-BP2, IGF-BP3), and nerve growth factor (NGF), amongst others . For transplantation, a biodegradable sponge composed of gelatin hydrogel (MedGel SP19) was used as a scaffold for OSCs. Preparations of OSCs + hydrogels, OSCs alone, hydrogel alone, and mock (growth medium alone) were randomly allocated to 4-week old mice subjected to facial nerve compression; these animals were left to recover and clinical evaluation for signs of facial nerve injury (by scoring their blinking and whisker movements) were followed immediately up to 14 days.

All animals achieved full recovery by 14 days after nerve compression injury, however those in the group that received both OSCs and hydrogels or OSCs alone had significant higher clinical scores than those in the hydrogel alone or mock group at earlier time points, reaching full recovery scores at 10 and 12 days respectively. Notably, those animals receiving OSCs seeded in hydrogels had superior functional recovery as evidenced by higher amplitudes in evoked compound muscle action potentials (CMAPs) measured in the buccinator muscle (one of the facial expression muscles innervated by the facial nerve) 14 days after injury. This effect was accompanied by increased number of regenerating fibers 7 and 14 days after facial nerve injury.

Overall, the Esaki et al. show us in this study the regenerative power of OSCs is not only confined to central nervous system injuries but also peripheral nervous system injuries, by providing trophic support and being able to differentiate into mature glia and neurons. Considering, human OSCs are self-replicating, form spheres, express neural stem cell and differentiation markers and can be readily isolated from olfactory mucosa biopsies, the findings shared by Esaki et al., open the door to further translational explorations using human OSCs in central and peripheral nervous system injuries.

By Juan C. Sanchez-Arias
PhD Candidate (UVic)