Human ciliary neurotrophic factor-overexpressing stable bone marrow stromal cells in the treatment of a rat model of traumatic spinal cord injury
Human ciliary neurotrophic factor-overexpressing stable bone marrow stromal cells in the treatment of a rat model of traumatic spinal cord injury
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DOI：
10.1016/j.jcyt.2015.03.689
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发表时间：
2015-07-01
期刊：
影响因子：
4.5
通讯作者：
Taheri, Taher
中科院分区：
文献类型：
--
作者：
Abbaszadeh, Hojjat-Allah;Tiraihi, Taki;Taheri, Taher
背景目标。中枢神经系统（CNS）的创伤性损伤常常引起运动功能障碍。然而，由于CNS的复杂性和临床表现的可变性，修复受损的CNS组织和恢复其功能的努力是特别苛刻的。另一方面，再生治疗领域的最新进展导致了治疗创伤性CNS损伤的新方法，并重新燃起了克服障碍的希望。看来轴突再生长抑制分子和轴突再生长诱导分子之间的平衡决定了轴突再生长的命运。神经营养因子可以倾斜这种平衡，并确实促进细胞存活和轴突再生神经变性。睫状神经营养因子（CNTF）是近年来研究较多的神经营养因子之一。方法.我们转染大鼠骨髓基质干细胞与哺乳动物表达载体插入人CNTF基因通过使用非病毒的方法制备人CNTF-过表达干细胞在离体条件下。我们将这些修饰的细胞移植到大鼠脊髓创伤模型中，以探讨挫伤诱导后的功能恢复。结果我们从免疫细胞化学和行为测试的数据表明，这些细胞可以作为一个强大的潜在的方法来治疗创伤性中枢神经系统损伤，因为这些修饰的细胞改善了脊髓损伤大鼠模型的行为测试分数。结论.过量表达CNTF的骨髓基质细胞可改善脊髓创伤性损伤，有望用于治疗中枢神经系统创伤性损伤。
Background aims. Traumatic injury to the central nervous system (CNS) often causes motor dysfunctions. However, because of the CNS complexity and variability in the clinical presentations, efforts to repair damaged CNS tissue and restoring its functions are particularly demanding. On the other hand, recent progress in the regenerative therapy field have led to novel approaches for the treatment of traumatic CNS injury and renewed hopes to overcome the obstacles. It appears that the balance between neurite re-growth inhibiting and neurite re-growth inducing molecules determines the axonal re-growth fate. Neurotrophic factors can tilt this balance and indeed promote cell survival and axonal re-growth over neuro-degeneration. One of the promising neurotrophic factors in this field is ciliary neurotrophic factor (CNTF). Methods. We transfected rat bone marrow stromal cells with a mammalian expression vector inserted human CNTF gene through the use of a non-viral method to prepare human CNTF-overexpressing stem cells under ex vivo conditions. We transplanted these modified cells to the rat model of spinal cord traumatic injury to,explore functional recovery after contusion induction. Results. Our data from immunocytochemistry and behavioral tests showed that such cells can act as a powerful potential approach to treat traumatic CNS injuries because these modified cells improved the behavioral test scores in the rat model of spinal cord injury. Conclusions. CNTF-overexpressing bone marrow stromal cells can ameliorate spinal cord traumatic injury and can be used in the treatment of traumatic CNS injuries in the near future.