Department of Orthopedic Surgery, The Second Affiliated Hospital, Fujian Medical University, Quanzhou, Fujian Province, People's Republic of China.
PLoS One. 2013 May 2;8(5):e63444. doi: 10.1371/journal.pone.0063444. Print 2013.
This study aims to investigate the potentially protective effect of neuroglobin (Ngb) gene-modified bone marrow mesenchymal stem cells (BMSCs) on traumatic spinal cord injury (SCI) in rabbits.
A lentiviral vector containing an Ngb gene was constructed and used to deliver Ngb to BMSCs. Ngb gene-modified BMSCs were then injected at the SCI sites 24 hours after SCI. The motor functions of the rabbits were evaluated by the Basso-Beattie-Bresnahan rating scale. Fluorescence microscopy, quantitative real-time PCRs, Western blots, malondialdehyde (MDA) tests, and terminal deoxynucleotidyltransferase-mediated UTP end labeling assays were also performed.
Ngb expression in the Ngb-BMSC group increased significantly. A more significant functional improvement was observed in the Ngb-BMSC group compared with those in the other groups. Traumatic SCI seemingly led to an increase in MDA level and number of apoptotic cells, which can be prevented by Ngb-BMSC treatment.
This study demonstrates that Ngb gene-modified BMSCs can strengthen the therapeutic benefits of BMSCs in reducing secondary damage and improving the neurological outcome after traumatic SCI. Therefore, the combined strategy of BMSC transplantation and Ngb gene therapy can be used to treat traumatic SCI.
本研究旨在探讨神经球蛋白(Ngb)基因修饰的骨髓间充质干细胞(BMSCs)对兔创伤性脊髓损伤(SCI)的潜在保护作用。
构建了含有 Ngb 基因的慢病毒载体,并将 Ngb 基因递送至 BMSCs。在 SCI 后 24 小时将 Ngb 基因修饰的 BMSCs 注射到 SCI 部位。通过 Basso-Beattie-Bresnahan 评分量表评估兔子的运动功能。荧光显微镜、实时定量 PCR、Western blot、丙二醛(MDA)试验和末端脱氧核苷酸转移酶介导的 UTP 末端标记试验也进行了。
Ngb-BMSC 组的 Ngb 表达明显增加。与其他组相比,Ngb-BMSC 组的功能改善更为显著。创伤性 SCI 似乎导致 MDA 水平和凋亡细胞数量增加,而 Ngb-BMSC 治疗可以预防这种增加。
本研究表明,Ngb 基因修饰的 BMSCs 可以增强 BMSCs 减少继发性损伤和改善创伤性 SCI 后神经功能结局的治疗益处。因此,BMSC 移植和 Ngb 基因治疗的联合策略可用于治疗创伤性 SCI。