Gelatin-Coated Polycaprolactone Nanoparticle-Mediated Naringenin Delivery Rescue Human Mesenchymal Stem Cells from Oxygen Glucose Deprivation-Induced Inflammatory Stress

Ischemic stroke involves pro-inflammatory species, which implicates inflammation in the disease mechanism. Recent studies indicate that the prevalence of therapeutic choice such as stem cell transplantation has seen an upsurge in ischemic stroke. However, after transplantation the fate of transplanted cells is largely unknown. Human mesenchymal stem cells (MSCs), due to their robust survival rate upon transplantation in brain tissue, are being widely employed to treat ischemic stroke. In the present study, we have evaluated naringenin-loaded gelatin-coated polycaprolactone nanoparticles (nar-gel-c-PCLNPs) to rescue MSCs against oxygen glucose deprived insult. Naringenin, due to its strong anti-inflammatory effects, remains a therapeutic choice in neurological disorders. Though, the low solubility and inefficient delivery remain challenges in using naringenin as a therapeutic drug. The present study showed that inflammation occurred in MSCs during their treatment with oxygen glucose deprivation (OGD) and was well overturned by treatment with nar-gel-c-PCL NPs. In brief, the results indicated that nar-gel-c-PCL NPs were able to protect the loss of cell membrane integrity and restored neuronal morphology. Then nar-gel-c-PCL NPs successfully protected the human MSCs against OGD-induced inflammation as evident by reduced level of pro-inflammatory cytokine (TNF-alpha, IFN-gamma, and IL-1 beta) and other inflammatory biomarkers (COX2, iNOS, and MPO activity). Therefore, the modulation of inflammation by treatment with nar-gel-c-PCL NPs in MSCs could provide a novel strategy to improve MSC-based therapy, and thus, our nanoformulation may find a wide therapeutic application in ischemic stroke and other neuro-inflammatory diseases.