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

[41] Interferon-α2b reduces phosphorylation and activity of MEK and ERK through a Ras/Raf-independent mechanism [J].

Romerio, F. ;

Riva, A. ;

Zella, D. .

BRITISH JOURNAL OF CANCER, 2000, 83 (04) :532-538

[42] Human neural stem cells target and deliver therapeutic gene to experimental leptomeningeal medulloblastoma [J].

Shimato, S. ;

Natsume, A. ;

Takeuchi, H. ;

Wakabayashi, T. ;

Fujii, M. ;

Ito, M. ;

Ito, S. ;

Park, I. H. ;

Bang, J. H. ;

Kim, S. U. ;

Yoshida, J. .

GENE THERAPY, 2007, 14 (15) :1132-1142

[43] SPIN DIFFUSION MEASUREMENTS: SPIN ECHOES IN THE PRESENCE OF A TIME-DEPENDENT FIELD GRADIENT [J].

STEJSKAL, EO ;

TANNER, JE .

JOURNAL OF CHEMICAL PHYSICS, 1965, 42 (01) :288-+

[44] The CNS lesion scar:: new vistas on an old regeneration barrier [J].

Stichel, CC ;

Müller, HW .

CELL AND TISSUE RESEARCH, 1998, 294 (01) :1-9

[45] Intravenously transplanted human neural stem cells migrate to the injured spinal cord in adult mice in an SDF-1- and HGF-dependent manner [J].

Takeuchi, Hiroki ;

Natsume, Atsushi ;

Wakabayashi, Toshihiko ;

Aoshima, Chihiro ;

Shimato, Shinji ;

Ito, Motokazu ;

Ishii, Jun ;

Maeda, Yuka ;

Hara, Masahito ;

Kim, Seung U. ;

Yoshida, Jun .

NEUROSCIENCE LETTERS, 2007, 426 (02) :69-74

[46] Genetic manipulation of neural stem cells for transplantation into the injured spinal cord [J].

Tang, Bor Luen ;

Low, Choon Bing .

CELLULAR AND MOLECULAR NEUROBIOLOGY, 2007, 27 (01) :75-85

[47] Spontaneous and augmented growth of axons in the primate spinal cord: Effects of local injury and nerve growth factor-secreting cell grafts [J].

Tuszynski, MH ;

Grill, R ;

Jones, LL ;

McKay, HM ;

Blesch, A .

JOURNAL OF COMPARATIVE NEUROLOGY, 2002, 449 (01) :88-101

[48] Transplantation of human neural stem cells exerts neuroprotection in a rat model of Parkinson's disease [J].

Yasuhara, Takao ;

Matsukawa, Noriyuki ;

Hara, Koichi ;

Yu, Guolong ;

Xu, Lin ;

Maki, Mina ;

Kim, Seung U. ;

Borlongan, Cesario V. .

JOURNAL OF NEUROSCIENCE, 2006, 26 (48) :12497-12511

[49] IFN-α2b reduces IL-2 production and IL-2 receptor function in primary CD4+ T cells [J].

Zella, D ;

Romerio, F ;

Curreli, S ;

Secchiero, P ;

Cicala, C ;

Zagury, D ;

Gallo, RC .

JOURNAL OF IMMUNOLOGY, 2000, 164 (05) :2296-2302

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