Prolonged Expansion Induces Spontaneous Neural Progenitor Differentiation from Human Gingiva-Derived Mesenchymal Stem Cells

Neural crest-derived mesenchymal stem cells (MSCs) obtained from dental tissues received considerable interest in regenerative medicine, particularly in nerve regeneration owing to their embryonic origin and ease of harvest. Proliferation efficacy and differentiation capacity into diverse cell lineages propose dental MSCs as an in vitro tool for disease modeling. In this study, we investigated the spontaneous differentiation efficiency of dental MSCs obtained from human gingiva tissue (hGMSCs) into neural progenitor cells after extended passaging. At passage 41, the morphology of hGMSCs changed from typical fibroblast-like shape into sphere-shaped cells with extending processes. Next-generation transcriptomics sequencing showed increased expression of neural progenitor markers such as NES, MEIS2, and MEST. In addition, de novo expression of neural precursor genes, such as NRN1, PHOX2B, VANGL2, and NTRK3, was noticed in passage 41. Immunocytochemistry results showed suppression of neurogenesis repressors TP53 and p21, whereas Western blot results revealed the expression of neurotrophic factors BDNF and NT3 at passage 41. Our results showed the spontaneous efficacy of hGMSCs to differentiate into neural precursor cells over prolonged passages and that these cells may assist in producing novel in vitro disease models that are associated with neural development.