Yuan Xiaochen, Wu Qingbin, Wang Peng, Jing Yingli, Yao Haijiang, Tang Yinshan, Li Zhigang, Zhang Honggang, Xiu Ruijuan
Key Laboratory of Microcirculation, Ministry of Health, Institute of Microcirculation, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Orthopedics Department, Hebei Provincial Hospital of Traditional Chinese Medicine, Shijiazhuang, China.
Front Neurosci. 2019 Apr 16;13:319. doi: 10.3389/fnins.2019.00319. eCollection 2019.
Spinal cord injury (SCI) often leads to severe and permanent paralysis and places a heavy burden on individuals, families, and society. Until now, the therapy of SCI is still a big challenge for the researchers. Transplantation of mesenchymal stem cells (MSCs) is a hot spot for the treatment of SCI, but many problems and risks have not been resolved. Some studies have reported that the therapeutic effect of MSCs on SCI is related to the paracrine secretion of cells. The exosomes secreted by MSCs have therapeutic potential for many diseases. There are abundant pericytes which possess the characteristics of stem cells in the neurovascular unit. Due to the close relationship between pericytes and endothelial cells, the exosomes of pericytes can be taken up by endothelial cells more easily. There are fewer studies about the therapeutic potential of the exosomes derived from pericytes on SCI now. In this study, exosomes of pericytes were transplanted into the mice with SCI to study the restoration of motor function and explore the underlying mechanism. We found that the exosomes derived from pericytes could reduce pathological changes, improve the motor function, the blood flow and oxygen deficiency after SCI. In addition, the exosomes could improve the endothelial ability to regulate blood flow, protect the blood-spinal cord barrier, reduce edema, decrease the expression of HIF-1α, Bax, Aquaporin-4, and MMP2, increase the expression of Claudin-5, bcl-2 and inhibit apoptosis. The experiments proved that exosomes derived from pericytes could protect the barrier of spinal cord microvascular endothelial cells under hypoxia condition, which was related to PTEN/AKT pathway. In summary, our study showed that exosomes of pericytes had therapeutic prospects for SCI.
脊髓损伤(SCI)常导致严重且永久性的瘫痪,给个人、家庭和社会带来沉重负担。到目前为止,SCI的治疗对研究人员来说仍是一项巨大挑战。间充质干细胞(MSCs)移植是SCI治疗的一个热点,但许多问题和风险尚未得到解决。一些研究报道,MSCs对SCI的治疗作用与细胞的旁分泌有关。MSCs分泌的外泌体对多种疾病具有治疗潜力。在神经血管单元中存在大量具有干细胞特性的周细胞。由于周细胞与内皮细胞关系密切,周细胞的外泌体更容易被内皮细胞摄取。目前关于周细胞来源的外泌体对SCI治疗潜力的研究较少。在本研究中,将周细胞外泌体移植到SCI小鼠体内,以研究运动功能的恢复情况并探索其潜在机制。我们发现,周细胞来源的外泌体可以减轻SCI后的病理变化,改善运动功能、血流量和缺氧状况。此外,外泌体可以提高内皮细胞调节血流的能力,保护血脊髓屏障,减轻水肿,降低缺氧诱导因子-1α(HIF-1α)、Bax、水通道蛋白-4(Aquaporin-4)和基质金属蛋白酶2(MMP2)的表达,增加闭合蛋白-5(Claudin-5)、bcl-2的表达并抑制细胞凋亡。实验证明,周细胞来源的外泌体在缺氧条件下可保护脊髓微血管内皮细胞屏障,这与磷酸酶和张力蛋白同源物(PTEN)/蛋白激酶B(AKT)信号通路有关。综上所述,我们的研究表明周细胞外泌体对SCI具有治疗前景。