Kim Choonghyo, Kim Hee Jung, Lee Hyun, Lee Hanbyeol, Lee Seung Jin, Lee Seung Tae, Yang Se-Ran, Chung Chun Kee
Department of Neurosurgery, Kangwon National University School of Medicine, Chuncheon, Korea.
Divisions of Applied Animal Science and Animal Resource Science, Department of Animal Life Science, Kangwon National University, Chuncheon, Korea.
Int J Stem Cells. 2019 Jul 31;12(2):331-339. doi: 10.15283/ijsc18133.
Treatment with mesenchymal stem cells (MSC) in spinal cord injury (SCI) has been highlighted as therapeutic candidate for SCI. Although astrogliosis is a major phenomenon after SCI, the role of astrogliosis is still controversial. In this study, we determined whether acute transplantation of MSC improves the outcome of SCI through modulating astrogliosis.
Bone marrow derived rat MSCs were induced neural differentiation and transplanted after acute SCI rats. Matrix metalloproteinase (MMP) and neuro-inflammatory pathway were analyzed for acute astrogliosis at 1, 3 and 7 d after SCI in RT-PCR- and western blot analysis. Functional outcome was assessed serially at postoperative 1 d and weekly for 4 weeks. Histopathologic analysis was undertaken at 7 and 28 d following injury in immunohistochemistry.
Transplantation of MSCs decreased IL-1, CXCL-2, CXCL-10, TNF- and TGF- in a rat model of contusive SCI. Protein level of NF-B p65 was slightly decreased while level of STAT-3 was increased. In immunohistochemistry, MSC transplantation increased acute astrogliosis whereas attenuated scar formation with increased sparing white matter of spinal cord lesions. In RT-PCR analysis, mRNA levels of MMP2 was significantly increased in MSC transplanted rats. In BBB locomotor scale, the rats of MSC treated group exhibited improvement of functional recovery.
Transplantation of MSC reduces the inflammatory reaction and modulates astrogliosis via MMP2/STAT3 pathway leading to improve functional recovery after SCI in rats.
间充质干细胞（MSC）治疗脊髓损伤（SCI）已成为SCI治疗的候选方法。尽管星形胶质细胞增生是SCI后的主要现象，但其作用仍存在争议。在本研究中，我们确定急性移植MSC是否通过调节星形胶质细胞增生来改善SCI的预后。
将大鼠骨髓来源的MSC诱导神经分化后移植到急性SCI大鼠体内。在SCI后1、3和7天，通过逆转录聚合酶链反应（RT-PCR）和蛋白质印迹分析，分析基质金属蛋白酶（MMP）和神经炎症途径以评估急性星形胶质细胞增生情况。术后1天开始连续评估功能预后，术后4周每周评估一次。在损伤后7天和28天进行免疫组织化学组织病理学分析。
在大鼠挫伤性SCI模型中，MSC移植降低了白细胞介素-1（IL-1）、CXC趋化因子配体2（CXCL-2）、CXC趋化因子配体10（CXCL-10）、肿瘤坏死因子（TNF）和转化生长因子（TGF）水平。核因子-κB p65（NF-κB p65）蛋白水平略有下降，而信号转导和转录激活因子3（STAT-3）水平升高。免疫组织化学显示，MSC移植增加了急性星形胶质细胞增生，同时减轻了瘢痕形成，脊髓损伤灶白质保留增加。RT-PCR分析显示，MSC移植大鼠中MMP2的mRNA水平显著升高。在BBB运动评分中，MSC治疗组大鼠的功能恢复有所改善。
MSC移植通过MMP2/STAT3途径减少炎症反应并调节星形胶质细胞增生，从而改善大鼠SCI后的功能恢复。
