Granulocyte colony-stimulating factor (G-CSF) mobilizes bone marrow-derived cells into injured spinal cord and promotes functional recovery after compression-induced spinal cord injury in mice

被引:99
作者
Koda, Masao
Nishio, Yutaka
Kamada, Takahito
Someya, Yukio
Okawa, Akihiko
Mori, Chisato
Yoshinaga, Katsunori
Okada, Seiji
Moriya, Hideshige
Yamazaki, Masashi
机构
[1] Chiba Univ, Grad Sch Med, Dept Orthopaed Surg, Chuo Ku, Chiba 2608670, Japan
[2] Chiba Univ, Dept Bioenvironm Med, Chiba 2608670, Japan
[3] Chiba Rehabil Ctr, Chiba, Japan
[4] Kumamoto Univ, Ctr AIDS Res, Div Hematopoiesis, Kumamoto, Japan
关键词
granulocyte colony stimulating factor (G-CSF); spinal cord injury; bone marrow-derived cell; functional recovery;
D O I
10.1016/j.brainres.2007.02.058
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The aim of the present study was to elucidate the effects of granulocyte colony-stimulating factor (G-CSF)-mediated mobilization of bone marrow-derived stem cells on the injured spinal cord. Bone marrow cells of green fluorescent protein (GFP) transgenic mice were transplanted into lethally irradiated C57BL/6 mice. Four weeks after bone marrow transplantation, spinal cord injury was produced by a static load (20 g, 5 min) at T8 level. G-CSF (200 mu g/kg/day) was injected subcutaneously for S days. Immunohistochemistry for GFP and cell lineage markers was performed to evaluate G-CSF-mediated mobilization of bone marrow-derived cells into injured spinal cord. Hind limb locomotor recovery was assessed for 6 weeks. Immunohistochemistry revealed that G-CSF increased the number of GFP-positive cells in injured spinal cord, indicating that bone marrow-derived cells were mobilized and migrated into injured spinal cord. The numbers of double positive cells for GFP and glial markers were larger in the G-CSF treated mice than in the control mice. Luxol Fast Blue staining revealed that G-CSF promoted white matter sparing. G-CSF treated mice showed significant recovery of hind limb function compared to that of the control mice. In conclusion, G-CSF showed efficacy for spinal cord injury treatment through mobilization of bone marrow-derived cells. (c) 2007 Elsevier B.V. All rights reserved.
引用
收藏
页码:223 / 231
页数:9
相关论文
共 33 条
[11]   Plasticity of marrow-derived stem cells [J].
Herzog, EL ;
Chai, L ;
Krause, DS .
BLOOD, 2003, 102 (10) :3483-3493
[12]   Marrow stromal cells form guiding strands in the injured spinal cord and promote recovery [J].
Hofstetter, CP ;
Schwarz, EJ ;
Hess, D ;
Widenfalk, J ;
El Manira, A ;
Prockop, DJ ;
Olson, L .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (04) :2199-2204
[13]   Transplantation of hematopoietic stem cells from the peripheral blood [J].
Jansen, J ;
Hanks, S ;
Thompson, JM ;
Dugan, MJ ;
Akard, LP .
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2005, 9 (01) :37-50
[14]   Transplantation of bone marrow stromal cell-derived Schwann cells promotes axonal regeneration and functional recovery after complete transection of adult rat spinal cord [J].
Kamada, T ;
Koda, M ;
Dezawa, M ;
Yoshinaga, K ;
Hashimoto, M ;
Koshizuka, S ;
Nishio, Y ;
Morlya, H ;
Yamazaki, M .
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 2005, 64 (01) :37-45
[15]   Administration of hematopoietic cytokines in the subacute phase after cerebral infarction is effective for functional recovery facilitating proliferation of intrinsic neural stem/progenitor cells and transition of bone marrow-derived neuronal cells [J].
Kawada, H ;
Takizawa, S ;
Takanashi, T ;
Morita, Y ;
Fujita, J ;
Fukuda, K ;
Takagi, S ;
Okano, H ;
Ando, K ;
Hotta, T .
CIRCULATION, 2006, 113 (05) :701-710
[16]   Nonhematopoletic mesenchymal stem cells can be mobilized and differentiate into cardiomyocytes after myocardial infarction [J].
Kawada, H ;
Fujita, J ;
Kinjo, K ;
Matsuzaki, Y ;
Tsuma, M ;
Miyatake, H ;
Muguruma, Y ;
Tsuboi, K ;
Itabashi, Y ;
Ikeda, Y ;
Ogawa, S ;
Okano, H ;
Hotta, T ;
Ando, K ;
Fukuda, K .
BLOOD, 2004, 104 (12) :3581-3587
[17]   Hematopoietic stem cell and marrow stromal cell for spinal cord injury in mice [J].
Koda, M ;
Okada, S ;
Nakayama, T ;
Koshizuka, S ;
Kamada, T ;
Nishio, Y ;
Someya, Y ;
Yoshinaga, K ;
Okawa, A ;
Moriya, H ;
Yamazaki, M .
NEUROREPORT, 2005, 16 (16) :1763-1767
[18]   Transplanted hematopoietic stem cells from bone marrow differentiate into neural lineage cells and promote functional recovery after spinal cord injury in mice [J].
Koshizuka, S ;
Okada, S ;
Okawa, A ;
Koda, M ;
Murasawa, M ;
Hashimoto, M ;
Kamada, T ;
Yoshinaga, K ;
Murakami, M ;
Moriya, H ;
Yamazaki, M .
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY, 2004, 63 (01) :64-72
[19]  
NICOLA NA, 1983, J BIOL CHEM, V258, P9017
[20]   Selective activation of STAT3 in human monocytes stimulated by G-CSF:: implication in inhibition of LPS-induced TNF-α production [J].
Nishiki, S ;
Hato, F ;
Kamata, N ;
Sakamoto, E ;
Hasegawa, T ;
Kimura-Eto, A ;
Hino, M ;
Kitagawa, S .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 2004, 286 (06) :C1302-C1311