Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder. It is characterized by the accumulation of misfolded α-synuclein (α-syn) and progressive loss of dopaminergic neurons in the substantia nigra. Due to the limitations of current therapies, mesenchymal stromal cell (MSC) transplantation has emerged as a promising neuroprotective strategy. This study evaluated the neuroprotective potential of decidua-derived mesenchymal stromal cells (DMSCs) in vitro using a human neuroblastoma cell line (NB69) exposed to the neurotoxin 1-methyl-4-phenylpyridinium (MPP+) as a PD model. The NB69 cells were differentiated into a mature dopaminergic phenotype using dibutyryl cyclic adenosine monophosphate (dbcAMP) and then exposed to MPP+. In proliferative NB69 cells, the effect of DMSCs was masked by their inherent antitumor activity against the neuroblastoma phenotype. Conversely, in the differentiated NB69 model, DMSCs demonstrated a significant protective role against MPP+-induced cytotoxicity. Interestingly, the mechanism by which DMSCs might exert a neuroprotective effect against MPP+ damage in differentiated NB69 cells appears to involve improving mitochondrial function by reducing free radicals. In summary, these findings suggest that DMSCs 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.

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.