Abstract
Polydopamine nanoparticles are artificial melanin nanoparticles (MNPs) that show strong antioxidant activity. The effects of MNPs on the neuroprotection of mesenchymal stem cells (MSCs) against hypoxic-ischemic injury and the underlying mechanism have not yet been revealed. In this study, an oxygen-glucose deprivation (OGD)-injured neuron model was used to mimic neuronal hypoxic-ischemic injury in vitro. MSCs pretreated with MNPs and then cocultured with OGD-injured neurons were used to investigate the potential effects of MNPs on the neuroprotection of MSCs and to elucidate the underlying mechanism. After coculturing with MNPs-pretreated MSCs, MSCs, and MNPs in a transwell coculture system, the OGD-injured neurons were rescued by 91.24%, 79.32%, and 59.97%, respectively. Further data demonstrated that MNPs enhanced the neuroprotection against hypoxic-ischemic injury of MSCs by scavenging reactive oxygen species and superoxide and attenuating neuronal apoptosis by deactivating caspase-3, downregulating the expression of proapoptotic Bax proteins, and upregulating the expression of antiapoptotic Bcl-2 proteins. These findings suggest that MNPs enhance the neuroprotective effect of MSCs against hypoxic-ischemic injury by inhibiting apoptosis and upregulating antioxidant defense, which could provide some evidence for the potential application of combined MNPs and MSCs in the therapy for ischemic stroke.