Melanin nanoparticles enhance the neuroprotection of mesenchymal stem cells against hypoxic-ischemic injury by inhibiting apoptosis and upregulating antioxidant defense.

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.