Cheng Zhijian, Bosco Dale B, Sun Li, Chen Xiaoming, Xu Yunsheng, Tai Wenjiao, Didier Ruth, Li Jinhua, Fan Jianqing, He Xijing, Ren Yi
Cell Transplant. 2017 Mar 13;26(3):469-482. doi: 10.3727/096368916X693473. Epub 2016 Oct 12.
Spinal cord injury (SCI) causes functional impairment as a result of the initial injury followed by secondary injury mechanism. SCI provokes an inflammatory response that causes secondary tissue damage and neurodegeneration. While the use of neural stem cell (NSC) engraftment to mitigate secondary injury has been of interest to many researchers, it still faces several limitations. As such, we investigated if NSC-conditioned medium (NSC-M) possesses therapeutic potential for the treatment of SCI. It has been proposed that many of the beneficial effects attributed to stem cell therapies are due to secreted factors. Utilizing primary cell culture and murine models of SCI, we determined that systemic treatment with NSC-M was able to significantly improve motor function and lesion healing. In addition, NSC-M demonstrated significant anti-inflammatory potential in vitro and in vivo, reducing inflammatory cytokine expression in both activated macrophages and injured spinal cord tissues. NSC-M was also able to reduce the expression of inducible nitric oxide synthase (iNOS) within the spleen of injured animals, indicating an ability to reduce systemic inflammation. Thus, we believe that NSC-M offers a possible alternative to direct stem cell engraftment for the treatment of SCI.
脊髓损伤(SCI)由于初始损伤及继发损伤机制而导致功能障碍。SCI引发炎症反应,进而造成继发性组织损伤和神经变性。虽然许多研究人员对使用神经干细胞(NSC)移植来减轻继发性损伤感兴趣,但该方法仍面临一些局限性。因此,我们研究了NSC条件培养基(NSC-M)是否具有治疗SCI的潜力。有人提出,干细胞疗法的许多有益效果归因于分泌因子。利用原代细胞培养和SCI小鼠模型,我们确定用NSC-M进行全身治疗能够显著改善运动功能和损伤愈合。此外,NSC-M在体外和体内均显示出显著的抗炎潜力,可降低活化巨噬细胞和受损脊髓组织中炎性细胞因子的表达。NSC-M还能够降低受伤动物脾脏中诱导型一氧化氮合酶(iNOS)的表达,表明其具有减轻全身炎症的能力。因此,我们认为NSC-M为治疗SCI提供了一种可能替代直接干细胞移植的方法。