Comparative Study of the Protective and Neurotrophic Effects of Neuronal and Glial Progenitor Cells-Derived Conditioned Media in a Model of Glutamate Toxicity In Vitro

Abstract

Cell therapy represents a promising approach to the treatment of neurological diseases, offering potential benefits not only by cell replacement but also through paracrine secretory activities. However, this approach includes a number of limiting factors, primarily related to safety. The use of conditioned stem cell media can serve as an equivalent to cell therapy while avoiding its disadvantages. The present study was a comparative investigation of the antioxidant, neuroprotective and neurotrophic effects of conditioned media obtained from neuronal and glial progenitor cells (NPC-CM and GPC-CM) on the PC12 cell line in vitro. Neuronal and glial progenitor cells were obtained from iPSCs by directed differentiation using small molecules. GPC-CM reduced apoptosis, ROS levels and increased viability, expressions of the antioxidant response genes HMOX1 and NFE2L2 in a model of glutamate-induced oxidative stress. The neurotrophic effect was evidenced by a change in the morphology of pheochromocytoma cells to a neuron-like phenotype. Moreover, neurite outgrowth, expression of GAP43, TUBB3, MAP2, SYN1 genes and increased levels of the corresponding MAP2 and TUBB3 proteins. Treatment with NPC-CM showed moderate antiapoptotic effects and improved cell viability. This study demonstrated the potential application of CM in the field of regenerative medicine.