Human Dental Pulp Stem Cells Differentiate into Oligodendrocyte Progenitors Using the Expression of Olig2 Transcription Factor

Abstract

The helix-loop-helix transcription factor Olig2 is essential for lineage determination of oligodendrocytes. Differentiation of stem cells into oligodendrocytes and transplanting them is a novel strategy for the repair of different demyelination diseases. Dental pulp stem cells (DPSCs) are of great interest in regenerative medicine due to their potential for repairing damaged tissues. In this study, DPSCs were isolated from human third molars and transfected with the human Olig2 gene as a differentiation inducer for the oligodendrogenic pathway. Following the differentiation procedure, the expression of Sox2, NG2, PDGFRα, Nestin, MBP, Olig2, Oct4, glial fibrillary acidic protein and A2B5 as stage-specific markers was studied by real-time RT-qPCR, immunocytochemistry and Western blot analysis. The cells were transplanted into a mouse model of local sciatic damage by lysolecithin as a model for demyelination. Oligodendrocyte progenitor cells (OPCs) actively remyelinated and recovered the lysolecithin-induced damages in the sciatic nerve as revealed by treadmill exercise, the von Frey filament test and hind paw withdrawal in response to a thermal stimulus. Recovery of behavioral reflexes occurred 2-6 weeks after OPC transplantation. The results demonstrate that the expression of Olig2 in DPSCs reduces the expression of stem cell markers and induces the development of oligodendrocyte progenitors as revealed by the emergence of oligodendrocyte markers. DPSCs could be programmed into oligodendrocyte progenitors and considered as a simple and valuable source for the cell therapy of neurodegenerative diseases.