Interferon-β Delivery Via Human Neural Stem Cell Abates Glial Scar Formation in Spinal Cord Injury

被引：29

作者：

Nishimura, Yusuke ^{[1
]}

Natsume, Atsushi ^{[1
]}

Ito, Motokazu ^{[1
]}

Hara, Masahito ^{[1
]}

Motomura, Kazuya ^{[1
]}

Fukuyama, Ryuichi ^{[2
]}

Sumiyoshi, Naoyuki ^{[2
]}

Aoki, Ichio ^{[3
]}

Saga, Tsuneo ^{[3
]}

Lee, Hong J. ^{[4
]}

Wakabayashi, Toshihiko ^{[1
]}

Kim, Seung U. ^{[4
,5
]}

机构：

[1] Nagoya Univ, Dept Neurosurg, Nagoya, Aichi 4668550, Japan

[2] Konan Kosei Hosp, Div Pathol, Aichi, Japan

[3] Natl Inst Radiol Sci, Mol Imaging Ctr, MR Mol Imaging Team, Chiba 260, Japan

[4] Chung Ang Univ, Coll Med, Med Res Inst, Seoul 156756, South Korea

[5] Univ British Columbia, UBC Hosp, Dept Med, Div Neurol, Vancouver, BC, Canada

来源：

CELL TRANSPLANTATION | 2013年 / 22卷 / 12期

关键词：

Human neural stem cells (NSCs); Interferon-beta (INF-beta) gene; Spinal cord injury (SCI); Toll-like receptor 4 (TLR4); PROMOTES FUNCTIONAL RECOVERY; FIBER TRACKING; BRAIN TRANSPLANTATION; REACTIVE ASTROCYTES; THERAPEUTIC GENE; WHITE-MATTER; IFN-BETA; TARGET; ERK; REGENERATION;

D O I：

10.3727/096368912X657882

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Glial scar formation is the major impedance to axonal regrowth after spinal cord injury (SCI), and scar-modulating treatments have become a leading therapeutic goal for SCI treatment. In this study, human neural stem cells (NSCs) encoding interferon-beta (INF-beta) gene were administered intravenously to mice 1 week after SCI. Animals receiving NSCs encoding IFN-beta exhibited significant neurobehavioral improvement, electrophysiological recovery, suppressed glial scar formation, and preservation of nerve fibers in lesioned spinal cord. Systemic evaluation of SCI gliosis lesion site with lesion-specific microdissection, genome-wide microarray, and MetaCore pathway analysis identified upregulation of toll-like receptor 4 (TLR4) in SCI gliosis lesion site, and this led us to focus on TLR4 signaling in reactive astrocytes. Examination of primary astrocytes from TLR4 knockout mice, and in vivo inhibition of TLR4, revealed that the effect of IFN-beta on the suppression of glial scar formation in SCI requires TLR4 stimulation. These results suggest that IFN-beta delivery via intravenous injection of NSCs following SCI inhibits glial scar formation in spinal cord through stimulation of TLR4 signaling.

引用

页码：2187 / 2201

页数：15

共 49 条

[1] Neural stem cells display extensive tropism for pathology in adult brain: Evidence from intracranial gliomas [J].

Aboody, KS ;

Brown, A ;

Rainov, NG ;

Bower, KA ;

Liu, SX ;

Yang, W ;

Small, JE ;

Herrlinger, U ;

Ourednik, V ;

Black, PM ;

Breakefield, XO ;

Snyder, EY .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (23) :12846-12851

[2] Basso mouse scale for locomotion detects differences in recovery after spinal cord in ury in five common mouse strains [J].

Basso, DM ;

Fisher, LC ;

Anderson, AJ ;

Jakeman, LB ;

McTigue, DM ;

Popovich, PG .

JOURNAL OF NEUROTRAUMA, 2006, 23 (05) :635-659

[3] Interferons at age 50: past, current and future impact on biomedicine [J].

Borden, Ernest C. ;

Sen, Ganes C. ;

Uze, Gilles ;

Silverman, Robert H. ;

Ransohoff, Richard M. ;

Foster, Graham R. ;

Stark, George R. .

NATURE REVIEWS DRUG DISCOVERY, 2007, 6 (12) :975-990

[4]

Ducreux D, 2006, AM J NEURORADIOL, V27, P214

[5]

Facon D, 2005, AM J NEURORADIOL, V26, P1587

[6] Reactive astrocytes protect tissue and preserve function after spinal cord injury [J].

Faulkner, JR ;

Herrmann, JE ;

Woo, MJ ;

Tansey, KE ;

Doan, NB ;

Sofroniew, MV .

JOURNAL OF NEUROSCIENCE, 2004, 24 (09) :2143-2155

[7] Effect of immunomodulation with human interferon-β on early functional recovery from experimental spinal cord injury [J].

Gok, Beril ;

Okutan, Ozerk ;

Beskonakli, Etem ;

Palaoglu, Selcuk ;

Erdamar, Husamettin ;

Sargon, Mustafa F. .

SPINE, 2007, 32 (08) :873-880

[8] Astrocyte TLR4 Activation Induces a Proinflammatory Environment Through the Interplay Between MyD88-Dependent NFκB Signaling, MAPK, and Jak1/Stat1 Pathways [J].

Gorina, Roser ;

Font-Nieves, Miriam ;

Marquez-Kisinousky, Leonardo ;

Santalucia, Tomas ;

Planas, Anna M. .

GLIA, 2011, 59 (02) :242-255

[9] Glial scar and neuroregeneration: histological, functional, and magnetic resonance imaging analysis in chronic spinal cord injury Laboratory investigation [J].

Hu, Rong ;

Zhou, Jianjun ;

Luo, Chunxia ;

Lin, Jiangkai ;

Wang, Xianrong ;

Li, Xiaoguang ;

Bian, Xiuwu ;

Li, Yunqing ;

Wan, Qi ;

Yu, Yanbing ;

Feng, Hua .

JOURNAL OF NEUROSURGERY-SPINE, 2010, 13 (02) :169-180

[10] Transplantation of human neural stem cells transduced with Olig2 transcription factor improves locomotor recovery and enhances myelination in the white matter of rat spinal cord following contusive injury [J].

Hwang, Dong H. ;

Kim, Byung G. ;

Kim, Eun J. ;

Lee, Seung I. ;

Joo, In S. ;

Suh-Kim, Haeyoung ;

Sohn, Seonghyang ;

Kim, Seung U. .

BMC NEUROSCIENCE, 2009, 10 :117

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