Anti-Inflammatory Mechanism of Neural Stem Cell Transplantation in Spinal Cord Injury.
Anti-Inflammatory Mechanism of Neural Stem Cell Transplantation in Spinal Cord Injury.
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DOI：
10.3390/ijms17091380
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发表时间：
2016-08-23
影响因子：
5.6
通讯作者：
He X
中科院分区：
文献类型：
--
作者：
Cheng Z;Zhu W;Cao K;Wu F;Li J;Wang G;Li H;Lu M;Ren Y;He X
神经干细胞(NSC)移植可促进脊髓损伤后功能恢复。然而，对神经干细胞如何发挥其治疗可塑性的机制缺乏详细的了解。将小鼠神经干细胞移植至脊髓损伤后7d，用Basso小鼠评分(BMS)评定运动功能。通过中性粒细胞和巨噬细胞免疫荧光染色及肿瘤坏死因子α、白介素1β、白介素6和白介素12mRNA水平的检测分析神经干细胞移植的抗炎作用。采用实时定量聚合酶链式反应分析诱导型一氧化氮合酶、肿瘤坏死因子α、白介素1β、白介素6和白介素10mRNA的表达水平。采用酶联免疫吸附试验检测骨髓基质细胞产生肿瘤坏死因子-α和白介素1-β的能力。移植的神经干细胞显著提高了BMS评分(p<；0.05)。组织学结果显示，移植的神经干细胞从注射部位向损伤区域迁移。神经干细胞移植可明显减少损伤区域中心的中性粒细胞和iNOS+/Mac-2+细胞的数量(p<；0.05)。同时，神经干细胞移植组肿瘤坏死因子-α、IL-1β、IL-6和IL-12mRNA水平较对照组显著降低。此外，神经干细胞在体外可抑制BMDM诱导型一氧化氮合酶的表达和巨噬细胞释放炎症因子(p<；0.05)。提示神经干细胞移植可能通过减少M1巨噬细胞的活化和中性粒细胞的渗入来调节脊髓损伤后的炎症反应，增强神经功能。因此，本研究为探讨脊髓损伤后神经干细胞移植抗炎作用的机制提供了新的思路。
Neural stem cell (NSC) transplantation has been proposed to promote functional recovery after spinal cord injury. However, a detailed understanding of the mechanisms of how NSCs exert their therapeutic plasticity is lacking. We transplanted mouse NSCs into the injured spinal cord seven days after SCI, and the Basso Mouse Scale (BMS) score was performed to assess locomotor function. The anti-inflammatory effects of NSC transplantation was analyzed by immunofluorescence staining of neutrophil and macrophages and the detection of mRNA levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and interleukin-12 (IL-12). Furthermore, bone marrow-derived macrophages (BMDMs) were co-cultured with NSCs and followed by analyzing the mRNA levels of inducible nitric oxide synthase (iNOS), TNF-α, IL-1β, IL-6 and IL-10 with quantitative real-time PCR. The production of TNF-α and IL-1β by BMDMs was examined using the enzyme-linked immunosorbent assay (ELISA). Transplanted NSCs had significantly increased BMS scores (p < 0.05). Histological results showed that the grafted NSCs migrated from the injection site toward the injured area. NSCs transplantation significantly reduced the number of neutrophils and iNOS+/Mac-2+ cells at the epicenter of the injured area (p < 0.05). Meanwhile, mRNA levels of TNF-α, IL-1β, IL-6 and IL-12 in the NSCs transplantation group were significantly decreased compared to the control group. Furthermore, NSCs inhibited the iNOS expression of BMDMs and the release of inflammatory factors by macrophages in vitro (p < 0.05). These results suggest that NSC transplantation could modulate SCI-induced inflammatory responses and enhance neurological function after SCI via reducing M1 macrophage activation and infiltrating neutrophils. Thus, this study provides a new insight into the mechanisms responsible for the anti-inflammatory effect of NSC transplantation after SCI.
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影响因子：
2.6
作者：
Kim, Jaehyup;Hematti, Peiman
通讯作者：
Hematti, Peiman
促进巨噬细胞存活和功能的胚胎干细胞对于畸胎瘤的发展至关重要
影响因子：
7.3
作者：
Chen T;Wang X;Guo L;Wu M;Duan Z;Lv J;Tai W;Renganathan H;Didier R;Li J;Sun D;Chen X;He X;Fan J;Young W;Ren Y
通讯作者：
Ren Y
影响因子：
14.5
作者：
Lee, Soon-Tae;Chu, Kon;Roh, Jae-Kyu
通讯作者：
Roh, Jae-Kyu
DOI：
10.1093/brain/awr339
发表时间：
2012-02
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Cusimano M;Biziato D;Brambilla E;Donegà M;Alfaro-Cervello C;Snider S;Salani G;Pucci F;Comi G;Garcia-Verdugo JM;De Palma M;Martino G;Pluchino S
通讯作者：
Pluchino S
DOI：
10.1523/jneurosci.3257-09.2009
发表时间：
2009-10-28
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Kigerl KA;Gensel JC;Ankeny DP;Alexander JK;Donnelly DJ;Popovich PG
通讯作者：
Popovich PG