Transplantation of Galectin-1-Expressing Human Neural Stem Cells Into the Injured Spinal Cord of Adult Common Marmosets

被引:67
作者
Yamane, Junichi [1 ,2 ]
Nakamura, Masaya [2 ]
Iwanami, Akio [1 ,2 ,3 ]
Sakaguchi, Masanori [1 ]
Katoh, Hiroyuki [2 ,3 ]
Yamada, Masayuki [4 ,5 ]
Momoshima, Suketaka [6 ]
Miyao, Sachiyo [1 ,2 ]
Ishii, Ken [2 ]
Tamaoki, Norikazu [4 ]
Nomura, Tatsuji [4 ]
Okano, Hirotaka James [1 ]
Kanemura, Yonehiro [7 ]
Toyama, Yoshiaki [2 ]
Okano, Hideyuki [1 ]
机构
[1] Keio Univ, Sch Med, Dept Physiol, Shinjuku Ku, Tokyo 1608582, Japan
[2] Keio Univ, Sch Med, Dept Orthoped Surg, Shinjuku Ku, Tokyo 1608582, Japan
[3] Murayama Med Ctr, Natl Org, Div Res, Tokyo, Japan
[4] Cent Inst Expt Anim, Kawasaki Ku, Kanagawa, Japan
[5] Fujita Hlth Univ, Sch Hlth Sci, Fac Radiol Technol, Toyoake, Aichi, Japan
[6] Keio Univ, Sch Med, Dept Radiol, Shinjuku Ku, Tokyo 1608582, Japan
[7] Natl Hosp Org, Osaka Natl Hosp, Inst Clin Res, Osaka, Japan
关键词
spinal cord injury; galectin-1; common marmoset; neural stem/progenitor cells; preclinical study; VIVO GENE-TRANSFER; FUNCTIONAL RECOVERY; STEM/PROGENITOR CELLS; DOPAMINERGIC-NEURONS; NEUROTROPHIC FACTOR; ENDOGENOUS LECTIN; GALECTIN-1; GROWTH; PROLIFERATION; DIFFERENTIATE;
D O I
10.1002/jnr.22322
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Delayed transplantation of neural stem/progenitor cells (NS/PCs) into the injured spinal cord can promote functional recovery in adult rats and monkeys. To enhance the functional recovery after NS/PC transplantation, we focused on galectin-1, a carbohydrate-binding protein with pleiotropic roles in cell growth, differentiation, apoptosis, and neurite outgrowth. Here, to determine the combined therapeutic effect of NS/PC transplantation and galectin-1 on spinal cord injury (SCI), human NS/PCs were transfected by lentivirus with galectin-1 and green fluorescent protein (GFP), (Gal-NS/PCs) or GFP alone (GFP-NS/PCs), expanded in vitro, and then transplanted into the spinal cord of adult common marmosets, 9 days after contusive cervical SCI. The animals' motor function was evaluated by their spontaneous motor activity, bar grip power, and performance on a treadmill test. Histological analyses revealed that the grafted human NS/PCs survived and differentiated into neurons, astrocytes, and oligodendrocytes. There were significant differences in the myelinated area, corticospinal fibers, and serotonergic fibers among the Gal-NS/PC, GFP-NS/PC, vehicle-control, and sham-operated groups. The Gal-NS/PC-grafted animals showed a better performance on all the behavioral tests compared with the other groups. These findings suggest that Gal-NS/PCs have better therapeutic potential than NS/PCs for SCI in nonhuman primates and that human Gal-NS/PC transplantation might be a feasible treatment for human SCI. (C) 2010 Wiley-Liss, Inc.
引用
收藏
页码:1394 / 1405
页数:12
相关论文
共 65 条
  • [11] The use of a recombinant lentiviral vector for ex vivo gene transfer into the rat CNS
    Englund, U
    Ericson, C
    Rosenblad, C
    Mandel, RJ
    Trono, D
    Wictorin, K
    Lundberg, C
    [J]. NEUROREPORT, 2000, 11 (18) : 3973 - 3977
  • [12] Marrow stromal cells form guiding strands in the injured spinal cord and promote recovery
    Hofstetter, CP
    Schwarz, EJ
    Hess, D
    Widenfalk, J
    El Manira, A
    Prockop, DJ
    Olson, L
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (04) : 2199 - 2204
  • [13] Horie H, 1999, J NEUROSCI, V19, P9964
  • [14] Regenerating the damaged central nervous system
    Horner, PJ
    Gage, FH
    [J]. NATURE, 2000, 407 (6807) : 963 - 970
  • [15] Human neural stem/progenitor cells, expanded in long-term neurosphere culture, promote functional recovery after focal ischemia in Mongolian gerbils
    Ishibashi, S
    Sakaguchi, M
    Kuroiwa, T
    Yamasaki, M
    Kanemura, Y
    Shizuko, I
    Shimazaki, T
    Onodera, M
    Okano, H
    Mizusawa, H
    [J]. JOURNAL OF NEUROSCIENCE RESEARCH, 2004, 78 (02) : 215 - 223
  • [16] Galectin-1 regulates neurogenesis in the subventricular zone and promotes functional recovery after stroke
    Ishibashi, Satoru
    Kuroiwa, Toshihiko
    Sakaguchi, Masanori
    Sun, Liyuan
    Kadoya, Toshihiko
    Okano, Hideyuki
    Mizusawa, Hidehiro
    [J]. EXPERIMENTAL NEUROLOGY, 2007, 207 (02) : 302 - 313
  • [17] Establishment of graded spinal cord injury model in a nonhuman primate: The common marmoset
    Iwanami, A
    Yamane, J
    Katoh, H
    Nakamura, M
    Momoshima, S
    Ishii, H
    Tanioka, Y
    Tamaoki, N
    Nomura, T
    Toyama, Y
    Okano, H
    [J]. JOURNAL OF NEUROSCIENCE RESEARCH, 2005, 80 (02) : 172 - 181
  • [18] Transplantation of human neural stem cells for spinal cord injury in primates
    Iwanami, A
    Kaneko, S
    Nakamura, M
    Kanemura, Y
    Mori, H
    Kobayashi, S
    Yamasaki, M
    Momoshima, S
    Ishii, H
    Ando, K
    Tanioka, Y
    Tamaoki, N
    Nomura, T
    Toyama, Y
    Okano, H
    [J]. JOURNAL OF NEUROSCIENCE RESEARCH, 2005, 80 (02) : 182 - 190
  • [19] Identification of a neural stem cell in the adult mammalian central nervous system
    Johansson, CB
    Momma, S
    Clarke, DL
    Risling, M
    Lendahl, U
    Frisén, J
    [J]. CELL, 1999, 96 (01) : 25 - 34
  • [20] Galectin-1 promotes basal and kainate-induced proliferation of neural progenitors in the dentate gyrus of adult mouse hippocampus
    Kajitani, K.
    Nomaru, H.
    Ifuku, M.
    Yutsudo, N.
    Dan, Y.
    Miura, T.
    Tsuchimoto, D.
    Sakumi, K.
    Kadoya, T.
    Horie, H.
    Poirier, F.
    Noda, M.
    Nakabeppu, Y.
    [J]. CELL DEATH AND DIFFERENTIATION, 2009, 16 (03) : 417 - 427