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

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成果类型:
期刊论文
作者:
Nakajima, Hideaki;Uchida, Kenzo;Guerrero, Alexander Rodriguez;Watanabe, Shuji;Sugita, Daisuke;Takeura, Naoto;Yoshida, Ai;Long, Guang;Wright, Karina T.;Johnson, William E. B.;Baba, Hisatoshi
通讯作者:
Nakajima, H
作者机构:
[Takeura, Naoto; Uchida, Kenzo; Sugita, Daisuke; Guerrero, Alexander Rodriguez; Baba, Hisatoshi; Yoshida, Ai; Watanabe, Shuji; Nakajima, Hideaki] Univ Fukui, Dept Orthopaed & Rehabil Med, Fac Med Sci, Fukui 9101193, Japan.
[Wright, Karina T.] Keele Univ, Inst Sci & Technol Med, RJAH Orthopaed Hosp, Oswestry, Shrops, England.
[Long, Guang] Univ S China, Physiol Lab, Hengyang, Peoples R China.
[Johnson, William E. B.] Aston Univ, Birmingham B4 7ET, W Midlands, England.
通讯机构:
[Nakajima, H] Univ Fukui, Dept Orthopaed & Rehabil Med, Fac Med Sci, Matsuoka Shimoaizuki 23-3, Fukui 9101193, Japan.
语种:
英文
关键词:
bone marrow;macrophage;mesenchymal stem cell;spinal cord injury;transplantation
期刊:
JOURNAL OF NEUROTRAUMA
ISSN:
0897-7151
年:
2012
卷:
29
期:
8
页码:
1614-1625
文献类别:
WOS:Article
所属学科:
ESI学科类别:神经系统学&行为学;WOS学科类别:Clinical Neurology;Critical Care Medicine;Neurosciences
入藏号:
基金类别:
Ministry of Education, Science, and Culture of Japan [21591895, 21791389, 22390287, 23791631]; Japan Orthopaedics and Traumatology Foundation, Inc. [218]
机构署名:
本校为其他机构
摘要:
Mesenchymal stem cells (MSC) derived from bone marrow can potentially reduce the acute inflammatory response in spinal cord injury (SCI) and thus promote functional recovery. However, the precise mechanisms through which transplanted MSC attenuate inflammation after SCI are still unclear. The present study was designed to investigate the effects of MSC transplantation with a special focus on their effect on macrophage activation after SCI. Rats were subjected to T9-T10 SCI by contusion, then treated 3 days later with transplantation of 1.0 x 10(6) PKH26-labeled MSC into the contusion epicenter. 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, and reductions in TNF-alpha 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 sparing. 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.
参考文献:
Abrams MB, 2009, RESTOR NEUROL NEUROS, V27, P307, DOI 10.3233/RNN-2009-0480
Akiyama Y, 2002, J NEUROSCI, V22, P6623
Akiyama Y, 2002, GLIA, V39, P229, DOI 10.1002/glia.10102
Ankeny DP, 2004, EXP NEUROL, V190, P17, DOI 10.1016/J.expneurol.2004.05.045
Bai LH, 2009, GLIA, V57, P1192, DOI 10.1002/glia.20841

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