神经营养因子-3 基因修饰的骨髓间充质干细胞和水凝胶联合应用对脊髓损伤模型大鼠的治疗作用研究
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中国医学科学院医学实验动物研究所,北京协和医学院比较医学中心,北京 100021


Bone marrow mesenchymal stem cells modified with the neurotrophic factor-3 gene combined with hydrogels for the treatment of spinal cord injury in rats
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Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing 100021, China

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    摘要:

    目的 研究骨髓间充质干细胞( bone marrow mesenchymal stem cells, BMSC)、神经营养因子-3 (neurotrophic factor-3, NT-3)、水凝胶(hydrogels)对脊髓损伤的联合治疗作用。 方法 首先,培养大鼠 BMSC 基因修饰,使其过表达 NT-3,制作水凝胶并搭载细胞。然后,建立大鼠急性不完全性脊髓损伤模型并植入相应治疗。最后,术后通过运动行为学(Basso Beatlie Bresnahan, BBB 评分)和病理学检测其对脊髓损伤的治疗作用。结果 各个联合治疗组大鼠 BBB 评分均有不同程度增加,BMSC+NT-3+hydrogels 组治疗作用最为明显。免疫组织化学检测显示各个联合治疗组神经元、神经纤维数目均有不同程度增加,星形胶质细胞数目较少。 治疗组中,BMSC+NT-3+ hydrogels 组大鼠神经元、神经纤维数目最多,星形胶质细胞数目最少。 所有结果组间比较差异均有统计学意义(P < 0. 05)。 结论 细胞(BMSC)、因子(NT-3)和支架(hydrogels)在治疗脊髓损伤中相互促进,联合移植于急性不完全性脊髓损伤模型大鼠,可提升模型大鼠后肢运用行为能力;促进损伤后神经元和神经纤维再生与修复并抑制损伤节段胶质瘢痕形成。本研究提示,制备更完美、可注射的细胞+因子+支架的复合材料,可对脊髓损伤神经修复再生的治疗提供新的思路。

    Abstract:

    Objective To investigate the therapeutic effects of the combination of bone marrow mesenchymal stem cells ( BMSCs), neurotrophic factor 3 ( NT-3), and hydrogels on spinal cord injury. Methods Rat BMSCs were genetically modified to overexpress NT-3, and hydrogels were prepared and loaded with the modified cells. Then, a model of acute incomplete spinal cord injury in rats was established and treated. The combined therapeutic effect on spinal cord injury was assessed by postoperative motor behavior (Basso Beatlie Bresnahan (BBB) score) and spinal cord pathology. Results The motor behavioral BBB scores of rats in the combination therapy group were increased by various degrees, and the therapeutic effect of the BMSC+NT-3+hydrogel group was the most obvious. Immunohistochemistry showed that the degree of nerve recovery in the combined treatment group was higher than that in the spinal cord injury model group. The numbers of neurons and nerve fibers were increased in all combined treatment groups, while the number of astrocytes was decreased. In the treatment groups, the BMSC+NT-3+hydrogel group had the highest number of neurons and nerve fibers and the lowest number of astrocytes. The difference between all groups was statistically significant ( P < 0. 05 ). Conclusions BMSCs, NT-3, and a hydrogel scaffold promoted each other and can be combined to better treat spinal cord injury. By transplanting into rats with acute incomplete spinal cord injury, they promoted post-injury neuronal and nerve fiber repair and inhibited the formation of glial scars. The preparation of more effective and injectable composites may provide a new concept for nerve repair and regeneration in spinal cord injury.

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赵宣淇,张 钰,秦 川,张 玲.神经营养因子-3 基因修饰的骨髓间充质干细胞和水凝胶联合应用对脊髓损伤模型大鼠的治疗作用研究[J].中国比较医学杂志,2020,30(7):1~12.

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  • 收稿日期:2020-04-28
  • 在线发布日期: 2020-08-25
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