Huang Peng, Gebhart Nichole, Richelson Elliott, Brott Thomas G, Meschia James F, Zubair Abba C
Department of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, Florida, USA.
Department of Pharmacology and Psychiatry, Mayo Clinic, Jacksonville, Florida, USA.
Cytotherapy. 2014 Oct;16(10):1336-44. doi: 10.1016/j.jcyt.2014.05.007. Epub 2014 Jun 11.
After ischemic or hemorrhagic stroke, neurons in the penumbra surrounding regions of irreversible injury are vulnerable to delayed but progressive damage as a result of ischemia and hemin-induced neurotoxicity. There is no effective treatment to rescue such dying neurons. Mesenchymal stem cells (MSCs) hold promise for rescue of these damaged neurons. In this study, we evaluated the efficacy and mechanism of MSC-induced neuro-regeneration and immune modulation.
Oxygen-glucose deprivation (OGD) was used in our study. M17 neuronal cells were subjected to OGD stress then followed by co-culture with MSCs. Rescue effects were evaluated using proliferation and apoptosis assays. Cytokine assay and quantitative polymerase chain reaction were used to explore the underlying mechanism. Antibody and small molecule blocking experiments were also performed to further understand the mechanism.
We showed that M17 proliferation was significantly decreased and the rate of apoptosis increased after exposure to OGD. These effects could be alleviated via co-culture with MSCs. Tumor necrosis factor-α was found elevated after OGD stress and was back to normal levels after co-culture with MSCs. We believe these effects involve interleukin-6 and vascular endothelial growth factor signaling pathways.
Our studies have shown that MSCs have anti-inflammatory properties and the capacity to rescue injured neurons.
在缺血性或出血性中风后，不可逆损伤区域周围半暗带中的神经元易因缺血和血红素诱导的神经毒性而受到延迟但渐进性的损伤。目前尚无有效的治疗方法来挽救这些即将死亡的神经元。间充质干细胞（MSCs）有望挽救这些受损神经元。在本研究中，我们评估了MSCs诱导神经再生和免疫调节的疗效及机制。
本研究采用氧糖剥夺（OGD）法。将M17神经元细胞置于OGD应激下，然后与MSCs共培养。使用增殖和凋亡检测方法评估挽救效果。采用细胞因子检测和定量聚合酶链反应来探究潜在机制。还进行了抗体和小分子阻断实验以进一步了解机制。
我们发现，暴露于OGD后，M17细胞的增殖显著降低，凋亡率增加。与MSCs共培养可减轻这些影响。在OGD应激后发现肿瘤坏死因子-α升高，与MSCs共培养后恢复到正常水平。我们认为这些影响涉及白细胞介素-6和血管内皮生长因子信号通路。
我们的研究表明，MSCs具有抗炎特性和挽救受损神经元的能力。
