NMR metabolomics assessment of neural commitment of human dental pulp-derived stem cells

Mesenchymal stem cells, particularly those derived from dental pulp cells (DPSCs), hold promising potential for neuro-regenerative therapies due to their multipotency and accessibility. Neural differentiation is closely linked to cellular metabolic reprogramming, yet the specific metabolic shifts alterations involved in DPSC neurogenesis remain underexplored.

Neural commitment was induced by 14 days of differentiation with EGF and bFGF. Untargeted proton nuclear magnetic resonance (¹H NMR) metabolomics was performed to investigate the metabolic alterations occurring during the neural commitment of human DPSCs cells.

Following 14 days of differentiation with EGF and bFGF, DPSCs exhibited a marked decrease in mesenchymal markers (CD44, CD90, CD105) and an increase in neural markers (β3-tubulin, NFH), alongside morphological changes toward a neuron-like phenotype. Metabolomics analysis revealed changes in metabolite levels, including increased aspartic acid and phosphocholine and reduced alanine, glutamate, and myo-inositol. Exploratory lipid analyses, suggested increased fatty acid and triacylglycerol content together with a higher PUFA/MUFA ratio. Pathway enrichment analyses highlighted amino acid metabolism and phosphoinositide signaling as potentially relevant. Understanding these changes enhances our knowledge of stem cell differentiation and supports the therapeutic potential of DPSCs in neuro-regenerative medicine.

These findings provide a descriptive metabolic characterization of DPSC neural commitment and identify candidate metabolite changes associated with early neural differentiation. While the results support the occurrence of metabolic remodelling during neural induction, further studies integrating functional and flux-based approaches are required to define the biological significance of these alterations.