The National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha 410006, Hunan, P.R. China.
Hunan Provincical Key Laboratory of Neurorestoratology, The Second Affiliated Hospital Hunan Normal University, Changsha 410003, Hunan, P.R. China.
Aging (Albany NY). 2021 Apr 4;13(8):11234-11256. doi: 10.18632/aging.202807.
Cerebral ischemia/reperfusion injury causes a series of intricate cascade reactions in brain tissue causing apoptosis and proinflammatory programmed cell death known as pyroptosis of nerve cells. The dysfunction of target organelle mitochondria plays a key role in the process of neuronal apoptosis and pyroptosis. Mesenchymal stem cells (MSCs) have been widely used in the experimental or clinical treatment of various ischemic diseases, but the therapeutic efficacy of MSCs on cerebral ischemia-reperfusion injury need to be improved. We successfully cultured olfactory mucosa MSCs (OM-MSCs) to obtain a better source of seed cells. In this way, the therapeutic potential of OM-MSCs transplantation has been evaluated for ischemic stroke using an optimized culture scheme . Ischemic-hypoxic preconditioned OM-MSCs (IhOM-MSCs) were used to treat a neuron model of oxygen-glucose deprivation/reperfusion and the middle cerebral artery occlusion in rats. These results demonstrated that IhOM-MSCs mediated the upregulation of the downstream target genes GRP78 and Bcl-2 by miR-181a to protect mitochondrial function and inhibit apoptosis and pyroptosis of neurons in the ischemia/reperfusion injury model. Thus, IhOM-MSCs transplantation may be an effective therapy of ischemic stroke in the future.
脑缺血/再灌注损伤会导致脑组织内发生一系列复杂的级联反应,引起细胞凋亡和促炎程序性细胞死亡,即神经细胞的细胞焦亡。靶细胞器线粒体的功能障碍在神经元凋亡和细胞焦亡过程中起着关键作用。间充质干细胞(MSCs)已广泛应用于各种缺血性疾病的实验或临床治疗,但 MSCs 对脑缺血/再灌注损伤的治疗效果仍需提高。我们成功培养了嗅黏膜间充质干细胞(OM-MSCs),获得了更好的种子细胞来源。通过优化培养方案,评估了 OM-MSCs 移植治疗缺血性脑卒中的治疗潜力。采用缺血缺氧预处理的 OM-MSCs(IhOM-MSCs)治疗氧葡萄糖剥夺/再灌注诱导的神经元模型和大鼠大脑中动脉闭塞模型。这些结果表明,IhOM-MSCs 通过 miR-181a 介导下游靶基因 GRP78 和 Bcl-2 的上调,保护线粒体功能,抑制缺血再灌注损伤模型中神经元的凋亡和细胞焦亡。因此,IhOM-MSCs 移植可能是未来缺血性脑卒中的一种有效治疗方法。