Melatonin Enhances Neural Differentiation of Adipose-Derived Mesenchymal Stem Cells

Int J Mol Sci. 2024 Apr 30;25(9):4891. doi: 10.3390/ijms25094891.

Abstract

Adipose-derived mesenchymal stem cells (ASCs) are adult multipotent stem cells, able to differentiate toward neural elements other than cells of mesodermal lineage. The aim of this research was to test ASC neural differentiation using melatonin combined with conditioned media (CM) from glial cells. Isolated from the lipoaspirate of healthy donors, ASCs were expanded in a basal growth medium before undergoing neural differentiation procedures. For this purpose, CM obtained from olfactory ensheathing cells and from Schwann cells were used. In some samples, 1 µM of melatonin was added. After 1 and 7 days of culture, cells were studied using immunocytochemistry and flow cytometry to evaluate neural marker expression (Nestin, MAP2, Synapsin I, GFAP) under different conditions. The results confirmed that a successful neural differentiation was achieved by glial CM, whereas the addition of melatonin alone did not induce appreciable changes. When melatonin was combined with CM, ASC neural differentiation was enhanced, as demonstrated by a further improvement of neuronal marker expression, whereas glial differentiation was attenuated. A dynamic modulation was also observed, testing the expression of melatonin receptors. In conclusion, our data suggest that melatonin's neurogenic differentiation ability can be usefully exploited to obtain neuronal-like differentiated ASCs for potential therapeutic strategies.

Keywords: Schwann cells; adipose-derived mesenchymal stem cells; glial conditioned media; melatonin; melatonin receptors; neuronal differentiation; olfactory ensheathing cells.

MeSH terms

  • Adipose Tissue / cytology
  • Adult
  • Cell Differentiation* / drug effects
  • Cells, Cultured
  • Culture Media, Conditioned / pharmacology
  • Glial Fibrillary Acidic Protein / metabolism
  • Humans
  • Melatonin* / pharmacology
  • Mesenchymal Stem Cells* / cytology
  • Mesenchymal Stem Cells* / drug effects
  • Mesenchymal Stem Cells* / metabolism
  • Nestin / genetics
  • Nestin / metabolism
  • Neurogenesis / drug effects
  • Neuroglia / cytology
  • Neuroglia / drug effects
  • Neuroglia / metabolism
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism
  • Schwann Cells / cytology
  • Schwann Cells / drug effects
  • Schwann Cells / metabolism
  • Synapsins / metabolism

Substances

  • Melatonin
  • Culture Media, Conditioned
  • Nestin
  • Glial Fibrillary Acidic Protein
  • Synapsins