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
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