Secretome of Human Umbilical cord mesenchymal stem cells exerts protective impacts on the blood-brain barrier against alpha-synuclein aggregates using an in vitro model

The blood-brain barrier (BBB) is a highly developed endothelial microvessel network extended to almost all parts of the central nervous system (CNS) that tightly seals cell-to-cell contacts and plays a critical role in maintaining CNS homeostasis. It also protects neurons from factors present in systemic circulation and prevents pathogens from entering the brain. Conversely, BBB disruption can initiate multiple pathways of nerve damage. BBB injury contributes significantly to various neurodegenerative diseases, including Parkinsons disease (PD). PD is also characterized by aggregation of the protein alpha-synuclein (SN) to form intracellular inclusions. Recent studies have shown that due to their active secretions, mesenchymal stem cells (MSCs) can effectively relieve the severity of many neurological diseases. However, the impact of MSCs on BBB remains largely unclear. Here, we investigated the effect of Secretome extracted from MSCs on BBB when treated with toxic SN-aggregates (SN-AGs). For this purpose, MSCs were first isolated from Umbilical cord tissue (UC-MSC), and their secretome was collected. Then, the impact of the secretome on the cytotoxicity and inflammatory effects of SN-AGs was examined on hCMEC/D3 cells using in vitro BBB models produced by mono- and co-culture systems. We explored the effects of SN-AGs in the presence of UC-MSC secretome on permeability, TEER value, and cytokine/chemokine release. We found that the Secretome of UC-MSCs exerts protective effects by inhibiting the toxic effects of SN-AGs on the BBB. These results strongly support the potential of UC-MSCs secretome for cell-free PD therapy. We also present an improved method for isolation of MSCs from umbilical cord tissue, which we hope will facilitate further studies on the use of these cells. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=164 SRC="FIGDIR/small/562544v2_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@1322b73org.highwire.dtl.DTLVardef@c2c0f9org.highwire.dtl.DTLVardef@b4b02org.highwire.dtl.DTLVardef@169acd9_HPS_FORMAT_FIGEXP M_FIG C_FIG