Ahmad Anas, Fauzia Eram, Kumar Manish, Mishra Rakesh Kumar, Kumar Ajay, Khan Mohsin Ali, Raza Syed Shadab, Khan Rehan
Department of Nano-Therapeutics, Institute of Nano Science and Technology, Habitat Centre, Phase 10, Sector 64, Mohali, Punjab 160062, India.
Laboratory for Stem Cell & Restorative Neurology, Department of Biotechnology, Era's Lucknow Medical College Hospital, Sarfarazganj, Lucknow-226003, India.
ACS Biomater Sci Eng. 2019 Feb 11;5(2):683-695. doi: 10.1021/acsbiomaterials.8b01081. Epub 2018 Dec 24.
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-PCL NPs) 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-α, IFN-γ, and IL-1β) 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.
缺血性中风涉及促炎物质，这表明炎症参与了该疾病的发病机制。最近的研究表明，诸如干细胞移植等治疗选择在缺血性中风中的应用率有所上升。然而，移植后移植细胞的命运在很大程度上尚不清楚。人间充质干细胞（MSCs）由于在脑组织中移植后的存活率较高，正被广泛用于治疗缺血性中风。在本研究中，我们评估了载有柚皮素的明胶包被聚己内酯纳米颗粒（nar-gel-c-PCL NPs）对间充质干细胞免受氧葡萄糖剥夺损伤的保护作用。柚皮素因其强大的抗炎作用，仍是神经疾病的一种治疗选择。然而，柚皮素的低溶解度和低效递送仍然是将其用作治疗药物的挑战。本研究表明，间充质干细胞在氧葡萄糖剥夺（OGD）处理期间发生炎症，而用nar-gel-c-PCL NPs处理可有效逆转炎症。简而言之，结果表明nar-gel-c-PCL NPs能够保护细胞膜完整性的丧失并恢复神经元形态。然后，nar-gel-c-PCL NPs成功保护人间充质干细胞免受OGD诱导的炎症，这可通过促炎细胞因子（TNF-α、IFN-γ和IL-1β）水平降低以及其他炎症生物标志物（COX2、iNOS和MPO活性）得以证明。因此，用nar-gel-c-PCL NPs处理间充质干细胞来调节炎症可为改善基于间充质干细胞的治疗提供一种新策略，因此，我们的纳米制剂可能在缺血性中风和其他神经炎症性疾病中找到广泛的治疗应用。
