骨髓间充质干细胞与电针对大鼠横断脊髓中抑制分子的下调作用及其对轴突再生的促进作用。
Bone marrow mesenchymal stem cells and electroacupuncture downregulate the inhibitor molecules and promote the axonal regeneration in the transected spinal cord of rats.
机构信息
Division of Neuroscience, Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
出版信息
Cell Transplant. 2011;20(4):475-91. doi: 10.3727/096368910X528102. Epub 2010 Sep 30.
Our previous study has reported that electroacupuncture (EA) promotes survival, differentiation of bone marrow mesenchymal stem cells (MSCs), and functional improvement in spinal cord-transected rats. In this study, we further investigated the structural bases of this functional improvement and the potential mechanisms of axonal regeneration in injured spinal cord after MSCs and EA treatment. Five experimental groups, 1) sham control (Sham-control); 2) operated control (Op-control); 3) electroacupuncture treatment (EA); 4) MSCs transplantation (MSCs), and 5) MSCs transplantation combined with electroacupuncture (MSCs + EA), were designed for this study. Western blots and immunohistochemical staining were used to assess the fibrillary acidic protein (GFAP) and chondroitin sulfate proteoglycans (CSPGs) proteins expression. Basso, Beattie, Bresnahan (BBB) locomotion test, cortical motor evoked potentials (MEPs), and anterograde and retrograde tracing were utilized to assess cortical-spinal neuronal projection regeneration and functional recovery. In the MSCs + EA group, increased labeling descending corticospinal tract (CST) projections into the lesion site showed significantly improved BBB scales and enhanced motor evoked potentials after 10 weeks of MSCs transplant and EA treatment. The structural and functional recovery after MSCs + EA treatment may be due to downregulated GFAP and CSPGs protein expression, which prevented axonal degeneration as well as improved axonal regeneration.
在先前的研究中我们已经报道了电针对骨髓间充质干细胞(MSCs)的存活、分化以及脊髓横断大鼠的功能改善有促进作用。在本研究中,我们进一步探讨了电针治疗后 MSCs 移植改善脊髓损伤功能的结构基础,以及损伤脊髓中轴突再生的潜在机制。为此,我们设计了五个实验组:1)假手术对照组(Sham-control);2)手术对照组(Op-control);3)电针治疗组(EA);4)MSCs 移植组(MSCs);5)MSCs 移植结合电针治疗组(MSCs+EA)。我们使用 Western blot 和免疫组化染色来评估纤维酸性蛋白(GFAP)和软骨素硫酸盐蛋白聚糖(CSPGs)的蛋白表达。Basso、Beattie、Bresnahan(BBB)运动功能评分、皮质运动诱发电位(MEPs)以及顺行和逆行示踪用于评估皮质脊髓神经元投射的再生和功能恢复。在 MSCs+EA 组中,进入损伤部位的皮质脊髓束(CST)投射的标记增加,表明在 MSCs 移植和电针治疗 10 周后 BBB 评分显著提高,运动诱发电位增强。MSCs+EA 治疗后的结构和功能恢复可能归因于 GFAP 和 CSPGs 蛋白表达下调,这既防止了轴突变性,又促进了轴突再生。