Meijs Matthijs F L, Timmers Leonardus, Pearse Damien D, Tresco Patrick A, Bates Margaret L, Joosten Elbert A J, Bunge Mary Bartlett, Oudega Martin
The Miami Project to Cure Paralysis, University of Miami School of Medicine, Miami, Florida 33136, USA.
J Neurotrauma. 2004 Oct;21(10):1415-30. doi: 10.1089/neu.2004.21.1415.
It was investigated whether the addition of basic fibroblast growth factor (FGF-2) enhances the efficacy of a Schwann cell (SC) bridge to repair the transected spinal cord by assessing tissue sparing and neuronal survival near the graft-cord interfaces, axonal regeneration and myelination in the graft, and behavioral recovery up to 12 weeks post-grafting. Experimental animals received a bridge of SCs within fibrin containing 1 microg of FGF-2; control animals received a SC implant without FGF-2. Sparing of tissue in a 2.5-mm-long segment near the graft-cord borders was 69% in the rostral and 52% in the caudal cord at 6 weeks post-grafting, not significantly different from the control group. With FGF-2, survival of NeuN-positive cells was increased in the rostral cord: 24.4%, 20.4%, and 17.2% of the number of positive cells in the uninjured cord compared to 13.5%, 9.1%, and 8.9% in controls at 3, 6, and 12 weeks post-grafting, respectively. Similarly, in the caudal cord, survival of NeuN-positive cells was increased with FGF-2: 19.3%, 16.8%, and 14.5% compared to 10.8%, 5.6%, and 6.1% in controls. The staining intensity of glial fibrillary acidic protein was significantly higher at the interfaces of both cord stumps at 3 weeks with SC/FGF-2 grafts; chondroitin sulfate proteoglycan (CS-56) staining was more intense in the rostral cord but only at 6 weeks. Blood vessels in the FGF-2 grafts were larger and less regular in shape than those in control grafts. Axonal growth into the bridge was not improved by the addition of FGF-2. Retrogradely traced neurons were not found rostral to the implant, indicating that axons had not grown a few mm into the caudal spinal tissue. Recovery of hind limb function was similar in both groups. Despite the neuroprotective effects of FGF-2, improved effects on axonal regeneration and functional recovery were not observed.
通过评估移植体与脊髓界面附近的组织保留情况和神经元存活情况、移植体内的轴突再生和髓鞘形成情况以及移植后长达12周的行为恢复情况,研究了添加碱性成纤维细胞生长因子(FGF-2)是否能增强雪旺细胞(SC)桥接修复横断脊髓的效果。实验动物接受了含有1微克FGF-2的纤维蛋白内的SC桥接;对照动物接受了不含FGF-2的SC植入物。移植后6周,移植体与脊髓边界附近2.5毫米长节段的组织保留率在脊髓头端为69%,在脊髓尾端为52%,与对照组无显著差异。添加FGF-2后,脊髓头端NeuN阳性细胞的存活率增加:移植后3周、6周和12周,与未损伤脊髓中阳性细胞数量相比,分别为24.4%、20.4%和17.2%,而对照组分别为13.5%、9.1%和8.9%。同样,在脊髓尾端,添加FGF-2后NeuN阳性细胞的存活率增加:分别为19.3%、16.8%和14.5%,而对照组分别为10.8%、5.6%和6.1%。在移植后3周,使用SC/FGF-2移植时,两个脊髓残端界面处的胶质纤维酸性蛋白染色强度显著更高;硫酸软骨素蛋白聚糖(CS-56)染色在脊髓头端更强烈,但仅在6周时如此。FGF-2移植体内的血管比对照移植体内的血管更大且形状更不规则。添加FGF-2并未改善轴突向桥接内的生长。在植入物头端未发现逆行追踪的神经元,表明轴突未长入尾端脊髓组织几毫米。两组后肢功能的恢复情况相似。尽管FGF-2具有神经保护作用,但未观察到对轴突再生和功能恢复的改善作用。