Mesenchymal stem cell secretome restores monocrotophos induced toxicity in human neural progenitor cells

The attempts are being made to investigate the new approaches to identify and treat the chemical-induced neurotoxicity. The human mesenchymal stem cell (hMSC) secretome has been recognized as one of the promising approaches, as it is rich in bioactive factors that promote regeneration and neuroprotection. We examined the neuroprotective effects of stimulated and unstimulated hMSC-secretomes on human iPSC-derived neural progenitor cells (hNPCs) exposed to pesticide-monocrotophos (MCP). In-vitro assays were employed to assess the neuroprotective potential of MSC secretomes on hNPCs exposed to subtoxic concentrations of MCP. Comprehensive multi-omics analyses (proteomics and transcriptomics), bioenergetics assessments, and computational bioinformatics analyses were performed to elucidate the underlying molecular mechanisms and therapeutic effects. As anticipated, MCP exposure decreased viability, caused morphological changes, increased oxidative stress, and disrupted mitochondrial function in hNPCs. The treatment with MSC secretomes at 50 % concentration restored cell viability, morphology, and oxidative stress markers to near-normal levels. Bioenergetics analyses revealed significant improvements in mitochondrial oxygen consumption rates, ATP production, and spare respiratory capacity following secretome treatment, which was corroborated by proteomic analyses indicating restoration of mitochondrial protein expression and function. Transcriptomic profiling identified critical MCP-dysregulated miRNAs (including hsa-miR-138-5p and hsa-miR-219a-5p) and their inverse relationship with altered protein expression levels, highlighting the regulatory capacity of hMSC secretomes. The study demonstrates the therapeutic potential of MSC secretomes in mitigating chemical-induced developmental neurotoxicity by modulating oxidative stress, mitochondrial recovery, and miRNA-mediated signaling. Stimulated hMSC secretomes, which are enriched with bioactive molecules, showed enhanced efficacy, making them promising candidates for targeted therapies in chemical neurotoxicity interventions.