Huang Yan, Liu Jianyang, He Jialin, Tan Fengbo, Lu Ming, Yuan Fulai, Zhu Xuelin, Kong Lingyu
NHC Key Laboratory of Birth Defect for Research and Prevention (Hunan Provincial Maternal and Child Health Care Hospital), Changsha, Hunan 410008, PR China.
Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, PR China.
Heliyon. 2023 Jul 3;9(7):e17874. doi: 10.1016/j.heliyon.2023.e17874. eCollection 2023 Jul.
Oxidative stress is essential in brain injury after intracerebral hemorrhage (ICH). Ferroptosis, iron-dependent oxidative cell death, overwhelms the antioxidant system. Recently, Olfactory mucosa-derived mesenchymal stem cells (OM-MSCs) hold great potential for treating ferroptosis-mediated oxidative brain damage after ICH. However, massive grafted cell death, possibly caused by a hostile host brain microenvironment, lessens the effectiveness of OM-MSCs. Therefore, it is necessary to develop strategies to upregulate the therapeutic efficacy of OM-MSCs in ICH. Curcumin, a well-established traditional herbal substance, has potent antioxidant property. In the present study, curcumin preconditioning might enhance the anti-oxidative activity of OM-MSCs, thereby augmenting the therapeutic efficacy of OM-MSCs in ICH. In vitro model of ICH, we demonstrated that curcumin-preconditioned OM-MSCs co-culture is more effective in attenuating the cell injury, oxidative stress, and ferroptosis of neuronal cells compared to the native OM-MSCs treatment. In vivo model of ICH, transplantation of curcumin-preconditioned OM-MSCs also showed better neuroprotective effects. Moreover, curcumin pretreatment promoted the survival of OM-MSCs under a conditioned medium from hemin-insulted neurons by improving the anti-oxidative capacities of OM-MSCs. Collectively, our investigation suggested that curcumin preconditioning effectively enhanced the survival and neuroprotective effects of OM-MSCs in the ICH model by upregulating the anti-oxidative capacities of OM-MSCs. Curcumin-preconditioned OM-MSCs might be taken as a novel therapeutic strategy for treating ICH.
氧化应激在脑出血（ICH）后的脑损伤中至关重要。铁死亡，即铁依赖性氧化细胞死亡，会使抗氧化系统不堪重负。最近，嗅黏膜来源的间充质干细胞（OM-MSCs）在治疗ICH后铁死亡介导的氧化脑损伤方面具有巨大潜力。然而，大量移植细胞死亡，可能是由恶劣的宿主脑微环境引起的，这降低了OM-MSCs的有效性。因此，有必要制定策略来提高OM-MSCs在ICH中的治疗效果。姜黄素是一种公认的传统草药成分，具有强大的抗氧化特性。在本研究中，姜黄素预处理可能会增强OM-MSCs的抗氧化活性，从而提高OM-MSCs在ICH中的治疗效果。在ICH的体外模型中，我们证明，与天然OM-MSCs治疗相比，姜黄素预处理的OM-MSCs共培养在减轻神经元细胞的损伤、氧化应激和铁死亡方面更有效。在ICH的体内模型中，姜黄素预处理的OM-MSCs移植也显示出更好的神经保护作用。此外，姜黄素预处理通过提高OM-MSCs的抗氧化能力，促进了OM-MSCs在血红素损伤神经元条件培养基下的存活。总体而言，我们的研究表明，姜黄素预处理通过上调OM-MSCs的抗氧化能力，有效地增强了OM-MSCs在ICH模型中的存活和神经保护作用。姜黄素预处理的OM-MSCs可能是一种治疗ICH的新型治疗策略。
