The neuroprotective effect of human umbilical cord MSCs-derived secretome against α-synuclein aggregates on the blood-brain barrier.

The blood-brain barrier (BBB) is a specialized network that maintains central nervous system homeostasis. Disruption of the BBB can lead to neuronal damage and contribute to neurodegenerative diseases like Parkinson's disease (PD), characterized by alpha-synuclein (αSN) aggregation, which forms intracellular inclusions. Mesenchymal stem cells (MSCs) have shown promise in alleviating the severity of neurological diseases through their paracrine secretions. However, the impact of MSCs secretome on the BBB remains largely unclear. In this study, we investigated the effect of human umbilical cord-derived MSCs (hUC-MSCs) secretome on the BBB in the presence of toxic αSN-aggregates (αSN-AGs). Using in vitro BBB models established through mono- and co-culture systems of hCMEC/D3 cells, we assessed the influence of the secretome on the cytotoxicity and inflammatory responses induced by αSN-AGs. Our results demonstrate that the hUC-MSCs secretome exerts protective effects by mitigating the toxic effects of αSN-AGs on the BBB. Specifically, this study shows a notable reduction in cytotoxicity and inflammation. Our findings highlight the potential of hUC-MSCs secretome as a promising candidate for innovative, cell-free therapies in PD treatment. Furthermore, we propose an optimized method for isolating MSCs from umbilical cord tissue, aimed at facilitating future research on the therapeutic applications of these cells.