Globose basal cells for spinal cord regeneration

Abstract

Spinal cord injury (SCI) is a devastating condition with loss of motor and sensory functions below the injury level. Cell based therapies are experimented in pre-clinical studies around the world. Neural stem cells are located intra-cranially in subventricular zone and hippocampus which are highly invasive sources. The olfactory epithelium is a neurogenic tissue where neurogenesis takes place throughout the adult life by a population of stem/progenitor cells. Easily accessible olfactory neuroepithelial stem/progenitor cells are an attractive cell source for transplantation in SCI. Globose basal cells (GBCs) were isolated from rat olfactory epithelium, characterized by flow cytometry and immunohistochemically. These cells were further studied for neurosphere formation and neuronal induction. T10 laminectomy was done to create drop-weight SCI in rats. On the 9th day following SCI, 5 × 105 cells were transplanted into injured rat spinal cord. The outcome of transplantation was assessed by the Basso, Beattie and Bresnahan (BBB) locomotor rating scale, motor evoked potential and histological observation. GBCs expressed neural stem cell markers nestin, SOX2, NCAM and also mesenchymal stem cell markers (CD29, CD54, CD90, CD73, CD105). These cells formed neurosphere, a culture characteristics of NSCs and on induction, differentiated cells expressed neuronal markers βIII tubulin, microtubule-associated protein 2, neuronal nuclei, and neurofilament. GBCs transplanted rats exhibited hindlimb motor recovery as confirmed by BBB score and gastrocnemius muscle electromyography amplitude was increased compared to controls. Green fluorescent protein labelled GBCs survived around the injury epicenter and differentiated into βIII tubulin-immunoreactive neuron-like cells. GBCs could be an alternative to NSCs from an accessible source for autologous neurotransplantation after SCI without ethical issues.

The Efficiency of Neurospheres Derived from Human Wharton’s Jelly Mesenchymal Stem Cells for Spinal Cord Injury Regeneration in Rats

“…Likewise, olfactory epithelium cells from rats were induced to globose basal cells with NSs formation and then transplanted into SCI rats (contusion model). The result showed hindlimb motor recovery in rats at the end of 8 weeks after transplantation [ 21 ]. However, the MSCs transplanted group showed the regeneration of movement at 1 day before transplantation.…”

“…MSCs can also be transdifferentiated into neurospheres (NSs). NSs are spheres formed of neural stem/progenitor cell aggregates with the ability to differentiate into neuronal lineages [ 20 , 21 ]. In previous literature, NSs from fetal spinal cord cultures have been transplanted and treated for SCI in rats [ 22 ].…”

The roles and applications of neural stem cells in spinal cord injury repair

“…Current evidence suggests that NSCs from olfactory mucosa can facilitate SCI repair. The transplanted NSCs from rat olfactory mucosa survived and differentiated into neurons in the SCI lesion sites in a rat contusion SCI model at T10 level, with significant functional recovery after four weeks post-surgery ( Muniswami et al, 2017 ). NSCs can be conveniently extracted from human participants instead of experimental animals.…”

Functional Consequences of Keratan Sulfate Sulfation in Electrosensory Tissues and in Neuronal Regulation

“…[203][204][205][206] It has been proposed that OECs arise from the olfactory epithelium however fate-mapping techniques in chicks and genetic lineage experiments in mice, show that OECs actually originate from a neural crest cell lineage of common developmental heritage with Schwann cells. [207,208] Horizontal cells [209] and globose cells [210] in the basal olfactory epithelium and adult olfactory sphere cells [211,212] also have a multipotent progenitor cell status [213] and may be of use as neuroprogenitors in CNS repair. [209,211,214,215] Transplanted OECs are capable of remyelinating axons and promoting the regrowth of transected axons.…”