Bone marrow-derived mesenchymal stem cell (BMSC)
transplantation has emerged as a potential treatment for
ischemic stroke. Preconditioning with pharmacological agents before
cell transplantation has been shown to increase the efficiency of
cell therapy. In this study,
trehalose (Tre), an autophagy inducer, was used as a pharmacological agent to treat BMSCs, and the
neuroprotective effect of BMSCs preconditioned with Tre on
cerebral ischemia was assessed. BMSCs were treated in vitro with different concentrations of Tre. Immunofluorescence staining of LC3B was performed to detect autophagy, and Western blotting for LC3,
Beclin1, p-AMPK, and p-mTOR was performed. Flow cytometry and Western blotting analysis were performed to measure cell apoptosis in the presence of
hydrogen peroxide (H2O2).
Enzyme-linked
immunosorbent assay was used to test the secretion levels of
neurotrophic factors. An in vivo
ischemia/reperfusion model was generated by
middle cerebral artery occlusion in male Sprague Dawley rats, and Tre-preconditioned BMSCs were administered intralesionally 24 hours after ischemic injury. Histopathological examination and neurological function studies were conducted. In vitro, Tre promotes autophagy of BMSCs through the activation of the AMPK signal pathway. Tre protected BMSCs from H2O2-induced cell viability reduction and apoptosis. Moreover, Tre pretreatment increased the secretion of
brain-derived neurotrophic factor,
vascular endothelial growth factor, and
hepatocyte growth factor. In vivo, preconditioning with Tre could further enhance the survival of BMSCs, reduce
infarct size, alleviate cell apoptosis, abate vessel decrease, and ultimately improve functional recovery. Our study indicates that Tre can enhance the survival of BMSCs under oxidative stress and enhance BMSC-based treatment of
ischemia/reperfusion injury.