Cell models to evaluate oligodendrocyte lineage cell growth on biomaterials

Abstract

Oligodendrocyte lineage and neuronal cells are essential neural populations required for axonal remyelination after spinal cord injury (SCI). Injection of an exogenous cell population into the site of neural injury has posed translational barriers, such as greater than 95% cell death without the use of neural cell protective delivery systems. Additionally, there is a lack of biomaterials approved for human implantation which could act as a neural cell delivery system. Furthermore, majority of scaffolds often have an isotropic structure, and may lack the ability to direct and guide axonal growth and remyelination through the damaged regions in SCI.

This thesis demonstrates the growth and maturation of oligodendrocyte lineage cells in the FDA approved, neurosurgical grade, three-dimensional (3D) biomaterial DuraGen PlusTM when co-seeded with astrocytes, which act as a supportive cell population for oligodendrocyte lineage survival. This cellular construct showed potential for use as an implantable scaffold in neural injuries which may result in demyelination. Additionally, encapsulating neuronal enriched cells within DuraGen PlusTM demonstrated that the scaffold enables the maturation of neurons. However, future work is required to improve viability of the cells within the construct. There is scope to produce a pre differentiated neural circuit in the DuraGen PlusTM matrix that can be integrated into lesioned sites in the CNS to promote regeneration. Moreover, oligodendrocyte lineage cells were seeded onto a poly-L-caprolactone (PCL), 3D aligned Cellevate nanomatrix to demonstrate the cell alignment capabilities of the matrix. The findings show that Cellevate was able to sustain the survival and maturation of oligodendrocyte precursors (OPCs) and promoted the alignment of OPCs within the scaffold. It thereby mimicked the in vivo neuro-cytoarchitecture that would aid in guiding axonal remyelination. Oligodendrocyte cell alignment, however, was not as prominent in the matured constructs and hence, future work could focus on further scaffold modifications which may be required to enhance cellular alignment.