Human menstrual blood-derived stem cells promote functional recovery in a rat spinal cord hemisection model.

Human menstrual blood-derived stem cells promote functional recovery in a rat spinal cord hemisection model.
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人经血干细胞促进大鼠脊髓半切模型的功能恢复

DOI:
10.1038/s41419-018-0847-8
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发表时间:
2018-08-29
影响因子:
9
通讯作者:
Dong C
Dong C
中科院分区:
生物学1区
文献类型:
--
作者:
Wu Q;Wang Q;Li Z;Li X;Zang J;Wang Z;Xu C;Gong Y;Cheng J;Li H;Shen G;Dong C

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脊髓损伤(SCI)是一种预后不佳的疾病,在现有的治疗方法下,严重的自主运动和感觉障碍,因此迫切需要新的有效的治疗策略。月经血间充质干细胞(MenSCs)具有易获得、产量高、增殖潜力大等优点,被认为是一种很有前途的再生医学策略。本研究将骨髓间充质干细胞移植到不完全胸段(T10)脊髓损伤(SCI)大鼠体内,分别于术后7、14、28天处死大鼠。根据实验结果,我们发现骨髓间充质干细胞移植改善了后肢的运动功能。此外,HE染色显示,经MenSCs处理后,病变部位的空洞形成明显减少。此外,与未处理组相比,经MenSCs处理后,损伤部位MAP2阳性成熟神经元增多,核因子-200表达的轴突再生增多,而硫酸软骨素蛋白多糖(CSPGs)的表达减少。此外,免疫荧光、Western印迹和qRT-PCR方法显示,移植MenSCs后,损伤脊髓中脑源性神经营养因子(BDNF)的水平显著升高。定量逆转录聚合酶链式反应结果显示,MSC移植后炎性因子α和IL-1β受到抑制。阻断BDNF-TrkB信号通路可抑制大鼠后肢运动功能的改善和运动神经元胞体面积的增加。结果表明,MANSCs移植对大鼠脊髓半横断模型的康复有良好的治疗作用,主要是通过增强BDNF的表达来实现的。骨髓间充质干细胞移植可能为未来脊髓损伤患者提供一种新的治疗策略。
Spinal cord injury (SCI) is associated with a dismal prognosis including severe voluntary motor and sensory deficits in the presence of the current therapies, thus new and efficient treatment strategies are desperately required. Along with several advantages, such as easy accessibility, high-yield, potential of enormous proliferation, menstrual blood-derived mesenchymal stem cells (MenSCs) have been proposed as a promising strategy in regeneration medicine. In this study, the MenSCs were transplanted into incomplete thoracic (T10) spinal cord injury (SCI) rats, all rats were sacrificed at 7, 14, and 28 days after surgery. Based on the results, we found that MenSCs transplantation improved the hind limb motor function. Besides, H&E staining showed that MenSCs treatment markedly reduced cavity formation in the lesion site. Furthermore, treatment by MenSCs showed more MAP2-positive mature neurons, as well as axonal regeneration manifested by NF-200 and less expression of chondroitin sulfate proteoglycans (CSPGs) than the non-treatment in the lesion site. Additionally, immunofluorescence, Western blot, and qRT-PCR methods showed that levels of brain-derived neurotrophic factor (BDNF) were significantly higher in the injured spinal cord after implantation of MenSCs. Results of qRT-PCR indicated that inflammatory factors, including TNF-α and IL-1β were inhibited after MenSCs transplantation. The improved motor function of hind limb and the increased cell body area of motor neurons were suppressed by blocking of the BDNF-TrkB signaling. It was eventually revealed that MenSCs implantation had beneficial therapeutic effects on the rehabilitation of the rat spinal cord hemisection model, mainly by enhancing the expression of BDNF. MenSCs transplantation may provide a novel therapeutic strategy for patients with SCI in the future.
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