Luo Yongjun, Xu Tao, Liu Wei, Rong Yuluo, Wang Jiaxing, Fan Jin, Yin Guoyong, Cai Weihua
Department of Orthopaedics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Int J Neurosci. 2021 Feb;131(2):170-182. doi: 10.1080/00207454.2020.1734598. Epub 2020 Mar 29.
This study aims to explore the effects of exosomes derived from G protein-coupled receptor kinase 2 interacting protein 1 (GIT1)-overexpressing bone marrow mesenchymal stem cell (GIT1-BMSC-Exos) on the treatment of traumatic spinal cord injury (SCI) in a rat model.
All the rats underwent a T10 laminectomy. A weight-drop impact was performed using a 10-g rod from a height of 12.5 mm except the sham group. Rats with SCI were distributed into three groups randomly and then treated with tail vein injection of GIT1-BMSCs-Exos, BMSCs-Exos and PBS, respectively. The effects of GIT1-Exos on glutamate (GLU)-induced apoptosis were also evaluated by TUNEL staining.
The results showed that rats treated with GIT1-BMSCs-Exos had better functional behavioral recovery than those treated with PBS or BMSCs-Exos only. The overexpression of GIT1 in BMSCs-Exos not only restrained glial scar formation and neuroinflammation after SCI, but also attenuated apoptosis and promoted axonal regeneration in the injured lesion area. Neuronal cell death induced by GLU was controlled remarkably as well.
In conclusion, our study suggested that the application of GIT1-BMSCs-Exos may provide a novel avenue for traumatic SCI treatment.
本研究旨在探讨过表达G蛋白偶联受体激酶2相互作用蛋白1(GIT1)的骨髓间充质干细胞来源的外泌体(GIT1-BMSC-Exos)对大鼠创伤性脊髓损伤(SCI)治疗的影响。
所有大鼠均接受T10椎板切除术。除假手术组外,使用10 g的棒从12.5 mm高度进行重物坠落撞击。将脊髓损伤大鼠随机分为三组,分别尾静脉注射GIT1-BMSCs-Exos、BMSCs-Exos和PBS。还通过TUNEL染色评估GIT1-Exos对谷氨酸(GLU)诱导的细胞凋亡的影响。
结果显示,与仅用PBS或BMSCs-Exos治疗的大鼠相比,用GIT1-BMSCs-Exos治疗的大鼠功能行为恢复更好。BMSCs-Exos中GIT1的过表达不仅抑制了脊髓损伤后的胶质瘢痕形成和神经炎症,还减轻了损伤灶区域的细胞凋亡并促进了轴突再生。GLU诱导的神经元细胞死亡也得到了显著控制。
总之,我们的研究表明,应用GIT1-BMSCs-Exos可能为创伤性脊髓损伤的治疗提供一条新途径。