Extracellular vesicles containing upregulated HSP70 from heat shock pretreated human umbilical cord mesenchymal stem cells ameliorates sleep deprivation induced anxiety-like behavior and cognitive impairment in mice

The aim of this research was to explore the therapeutic capabilities of extracellular vehicles (EVs) derived from human umbilical cord mesenchymal stem cells (hUC-MSCs) that had been subjected to heat shock pretreatment, in treating psychiatric disorders induced by sleep deprivation in mice. The EVs were isolated and characterized, while Western blotting was utilized to assess the expression of exosomal markers and heat shock protein 70 (HSP70). To evaluate the impact of EV treatment on anxiety-like behavior and cognitive impairment in sleep-deprived (SD) mice, open field test, plus maze test and Y-maze task were conducted. Heat shock pretreatment significantly increased the expression of HSP70 in EVs. Administration of EVs from heat shock pretreated hUC-MSCs improved anxiety-like behavior and cognitive function in sleep-deprived mice. Furthermore, EV treatment promoted synaptic protein expression, HSP70 expression and inhibited neuroinflammation in the hippocampus of SD mice. Western blotting analysis also revealed that EV treatment reduced the levels of TLR4 and p65 in the hippocampus. EVs from heat shock-pretreated hUC-MSCs have therapeutic potential for sleep deprivation-induced psychiatric disorders by regulating neuroinflammation and synaptic function in mice.