Department of Biomedical Science, CHA Stem Cell Institute, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si 13488, Gyeonggi-do, Korea.
Department of Physical Therapy, Gachon University, 191 Hambakmoero, Yeonsu-gu, Incheon 21936, Korea.
Int J Mol Sci. 2021 Jun 28;22(13):6970. doi: 10.3390/ijms22136970.
The most common type of spinal cord injury is the contusion of the spinal cord, which causes progressive secondary tissue degeneration. In this study, we applied genetically modified human neural stem cells overexpressing BDNF (brain-derived neurotrophic factor) (F3.BDNF) to determine whether they can promote functional recovery in the spinal cord injury (SCI) model in rats. We transplanted F3.BDNF cells via intrathecal catheter delivery after a contusion of the thoracic spinal cord and found that they were migrated toward the injured spinal cord area by MR imaging. Transplanted F3.BDNF cells expressed neural lineage markers, such as NeuN, MBP, and GFAP and were functionally connected to the host neurons. The F3.BDNF-transplanted rats exhibited significantly improved locomotor functions compared with the sham group. This functional recovery was accompanied by an increased volume of spared myelination and decreased area of cystic cavity in the F3.BDNF group. We also observed that the F3.BDNF-transplanted rats showed reduced numbers of Iba1- and iNOS-positive inflammatory cells as well as GFAP-positive astrocytes. These results strongly suggest the transplantation of F3.BDNF cells can modulate inflammatory cells and glia activation and also improve the hyperalgesia following SCI.
最常见的脊髓损伤类型是脊髓挫裂伤,它会导致进行性的继发性组织退化。在这项研究中,我们应用过表达脑源性神经营养因子(BDNF)的基因修饰人神经干细胞(F3.BDNF),以确定它们是否能促进大鼠脊髓损伤(SCI)模型的功能恢复。我们在胸段脊髓挫裂伤后通过鞘内导管递送 F3.BDNF 细胞,发现它们通过磁共振成像向损伤的脊髓区域迁移。移植的 F3.BDNF 细胞表达神经谱系标志物,如 NeuN、MBP 和 GFAP,并与宿主神经元功能连接。与假手术组相比,F3.BDNF 移植组的运动功能明显改善。这种功能恢复伴随着髓鞘保留体积的增加和 F3.BDNF 组囊腔面积的减少。我们还观察到,F3.BDNF 移植组的 Iba1 和 iNOS 阳性炎症细胞以及 GFAP 阳性星形胶质细胞数量减少。这些结果强烈表明,F3.BDNF 细胞的移植可以调节炎症细胞和神经胶质细胞的激活,并改善 SCI 后的痛觉过敏。