The effects and mechanism of bone marrow stromal cells for spinalcord injury

骨髓基质细胞对脊髓损伤的作用及机制

• 批准号: 23791631
• 负责人: NAKAJIMA Hideaki
• 金额: $ 2.75万
• 依托单位: University of Fukui
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23791631/
• 关键词: 骨; 脊椎脊髄病学; 骨髄間質細胞; 脊髄損傷; 細胞移植; 神経再生; 急性脊髄損傷

The precise mechanisms through which transplanted MSC attenuate inflammation after SCI are still unclear. The transplanted MSC migrated within the injured spinal cord without differentiating into glial or neuronal elements. MSC transplantation was associated with marked changes in the SCI environment, with significant increases in IL-4 and IL-13 levels reductions in TNF-α and IL-6 levels. This was associated simultaneously with increased numbers of alternatively activated macrophages (M2 phenotype: arginase -1 or CD206-positive) and decreased numbers of classically activated macrophages (M1 phenotype: iNOS or CD16/32-positive). These changes were associated with functional locomotion recovery in the MSC transplanted group, which correlated with preserved axons, less scar tissue formation and increased myelin sparring. Our results suggested that acute transplantation of MSC after SCI modified the inflammatory environment by shifting the macrophage phenotype from M1 to M2, and that this may reduce the effects of the inhibitory scar tissue in the subacute/chronic phase after injury to provide a permissive environment for axonal extension and functional recovery.

移植的MSC减轻脊髓损伤后炎症的确切机制仍不清楚。移植的MSC在损伤的脊髓内迁移，没有分化为神经胶质或神经元成分。骨髓间充质干细胞移植与脊髓损伤环境的显著改变有关，IL-4和IL-13水平显著升高，肿瘤坏死因子-α和IL-6水平降低。这与交替激活的巨噬细胞数量增加(M2表型：精氨酸酶-1或CD206阳性)和经典激活的巨噬细胞数量减少(M1表型：iNOS或CD16/32阳性)同时相关。这些变化与MSC移植组的功能运动恢复有关，这与保留轴突、减少瘢痕组织形成和增加髓鞘稀疏有关。我们的结果表明，脊髓损伤后MSC的急性移植通过将巨噬细胞表型从M1转变为M2来改善炎症环境，这可能减少了损伤后亚急性/慢性期抑制性瘢痕组织的影响，为轴突伸展和功能恢复提供了允许的环境。

项目成果

Transplantation of Mesenchymal Stem Cells Promotes an Alternative Pathway of Macrophage Activation and Functional Recovery after Spinal Cord Injury

• DOI: 10.1089/neu.2011.2109
• 发表时间: 2012-05-01
• 期刊: JOURNAL OF NEUROTRAUMA
• 影响因子: 4.2
• 作者: Nakajima, Hideaki;Uchida, Kenzo;Baba, Hisatoshi
• 通讯作者: Baba, Hisatoshi

骨髄間質細胞移植が脊髄損傷後macrophageの動態に与える影響.

骨髓基质细胞移植对脊髓损伤后巨噬细胞动态的影响。

• 发表时间: 2012
• 作者: 中嶋秀明 ;内田研造 ;Alexander Rodriguez Guerrero;渡邉修司;杉田大輔;竹浦直人;吉田藍;馬場久敏;Nakajima H;中嶋秀明;中嶋秀明;中嶋秀明
• 通讯作者: 中嶋秀明

Tumor Necrosis Factor-α Antagonist Reduces Apoptosis of Neurons and Oligodendroglia in Rat Spinal Cord Injury

• DOI: 10.1097/brs.0b013e3181f014ec
• 发表时间: 2011-08-01
• 期刊: SPINE
• 影响因子: 3
• 作者: Chen, Ke-Bing;Uchida, Kenzo;Baba, Hisatoshi
• 通讯作者: Baba, Hisatoshi

Transplantation of mesenchymal stem cells drrived from bone marrow after spinal cord injury contribute functional recovery and tissue regeneration by promoting alternative pathway of macrophage activation.

脊髓损伤后移植来自骨髓的间充质干细胞，通过促进巨噬细胞激活的替代途径，有助于功能恢复和组织再生。

• 发表时间: 2012
• 作者: 中嶋秀明 ;内田研造 ;Alexander Rodriguez Guerrero;渡邉修司;杉田大輔;竹浦直人;吉田藍;馬場久敏;Nakajima H
• 通讯作者: Nakajima H

Blockade of interleukin-6 signaling inhibits the classic pathway and promotes an alternative pathway of macrophage activation after spinal cord injury in mice.

• DOI: 10.1186/1742-2094-9-40
• 发表时间: 2012-02-27
• 期刊: Journal of neuroinflammation
• 影响因子: 9.3
• 作者: Guerrero AR;Uchida K;Nakajima H;Watanabe S;Nakamura M;Johnson WE;Baba H
• 通讯作者: Baba H