Protective Effect of Placental Mesenchymal Stromal Cells in an In Vitro Model of Parkinson’s Disease Using Differentiated Neuroblastoma Cells

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder, characterized by the accumulation of misfolded α-synuclein (α-syn), with the progressive loss of dopaminergic neurons in the substantia nigra. Given the limitations of current therapies, mesenchymal stromal cell (MSC) transplantation has emerged as a promising neuroprotective strategy. This study evaluated the in vitro neuroprotective potential of decidua-derived mesenchymal stem cells (DMSC) using neurotoxin 1-methyl-4-phenylpyridinium (MPP+) neurotoxin-induced damage in a human neuroblastoma cell line (NB69) as a model for PD. NB69 cells were differentiated into a mature dopaminergic phenotype using dibutyryl cyclic adenosine monophosphate (dbcAMP) and subsequently exposed to the MPP+. In proliferative NB69 cells, the effect of DMSC was masked by their inherent anti-tumor activity against the neuroblastoma phenotype. Conversely, in the differentiated NB69 model, DMSC demonstrated a significant protective role against MPP+-induced cytotoxicity. It is interesting that the mechanism by which DMSCs exert a neuroprotective effect against MPP+ damage in differentiated NB69 cells could be through an improvement in mitochondrial function by reducing free radicals. In summary, these findings suggest that DMSC exert a neuroprotective effect in a dopaminergic-like context and highlight the importance of using differentiated cell models to accurately evaluate cell-based therapies for PD in the striatum.