The impact of umbilical cord’s mesenchymal stem cells-derived secretome on the cerebral microvascular endothelial cells exposed to oxidative stress

Disturbing the haemostasis of the blood-brain barrier (BBB) accompanies with losing the tight junctions, is increasing the pro-inflammatory factors and matrix metalloproteinase that directly implicates in various complex and cureless neuronal disorders such as Parkinson’s disease (PD), Alzheimer’s disease (AD), stroke, amyotrophic lateral sclerosis (ALS) and traumatic brain injury (TBI). In recent years, employing mesenchymal stem cells (MSCs) and their secretome converts to potential therapeutic approaches in regenerative medicine. MSCs secret neuroprotective factors such as chemokines, cytokines, and extracellular vehicles (EVs) in their culture medium collectively named secretome. In this study, we aimed to evaluate the effect of MSCs-conditioned medium (MSC-CM) on BBB toward oxidative stress. At first, with great efforts high pure MSCs was isolated from human umbilical cord (hUC-MSCs) tissue with the expanded method and the purity was confirmed by expression of positive cell surface markers (CD۴۴, CD۷۳, CD۲۹), and lack expression of negative markers (CD۳۴, CD۱۴, CD۴۵) using flow cytometry. The secretome was collected in sub-culture three from the serum-free medium after ۲۴ hours of incubation and then added to a monolayer of hCMEC/D۳ cell culture as a BBB model at different concentrations. The culture was treated with ۱۰۰ μM of H۲O۲ to induce ROS and also NaOH for induction of cell death in different manners including: ۴ hours pre-treatment, ۴ hours post-treatment, or simultaneous treatment of the reagents and secretome. The results indicated that secretome-derived UC-MSCs modulated the ROS level in the presence of oxidative reagent and also cell degeneration in a dose-dependent manner. Accordingly, it seems that UC-MSCs secretome possibly has an antioxidant potential and a supportive role on the brain’s endothelial cells.

کلیدواژه ها:

Blood brain barrier ، Human umbilical cord ، MSCs-conditioned medium ، Neuroprotective ، oxidative stress ، reactive oxygen species