Nanotechnology to improve oligodendroglial differentiation in neural stem cell cultures using hydrogels based on graphene derivatives and cerium oxide

Oxidative stress is a well-known repressor of stem cell division and self-renewal. In addition, the accumulation of reactive oxygen and nitrogen species in NSCs critically affects their differentiation, favouring the generation of astroglial cell lineages at the expense of neuronal and oligodendroglial ones. To overcome these limitations, we generated 3D-hydrogels with varying concentrations of graphene oxide (GO) and CeO₂ nanoparticles as scaffolds to support the culture and differentiation of NSCs. To fabricate the hydrogel, ascorbic acid (AsA) was used as a reducing agent of the GO sheets. Self-assembled three-dimensional hydrogels were characterised to assess the effects of AsA and CeO₂ nanoparticles in their morphology, mechanical properties and electrical conductivity, allowing the attachment and integration of neurosphere-derived NSCs and progenitor cells into the hydrogel thanks to its highly porous structure. Furthermore, we found that the hydrogel formulation containing CeO₂ nanoparticles was able to buffer the accumulation of reactive oxygen species in NSCs as assessed by 2′,7′-Dichlorodihydrofluorescein diacetate cell-permeable probe, thus improving cell survival and differentiation towards oligodendroglial lineage during the evolution of cell culture.

The results obtained pave the way for the development of functional scaffolds capable of interacting with stem cells and represent a promising strategy to improve current limitations of cell therapy.