Ex-vivo expanded human blood-derived CD133+ cells promote repair of injured spinal cord

被引:22
作者
Kamei, Naosuke [1 ,2 ]
Kwon, Sang-Mo [1 ,3 ]
Alev, Cantas [1 ,4 ]
Nakanishi, Kazuyoshi [2 ]
Yamada, Kiyotaka [2 ]
Masuda, Haruchika [5 ]
Ishikawa, Masakazu [2 ]
Kawamoto, Atsuhiko [1 ]
Ochi, Mitsuo [2 ]
Asahara, Takayuki [1 ,5 ]
机构
[1] Inst Biomed Res & Innovat, Grp Vasc Regenerat, Chuo Ku, Kobe, Hyogo 6500047, Japan
[2] Hiroshima Univ, Grad Sch Biomed Sci, Dept Orthopaed Surg, Minami Ku, Hiroshima 7348551, Japan
[3] Pusan Natl Univ, Sch Med, Dept Physiol, Lab Vasc Med & Stem Cell Biol,Med Res Inst, Yangsan 626870, Gyeongsangnam D, South Korea
[4] RIKEN Ctr Dev Biol, Lab Early Embryogenesis, Chuo Ku, Kobe, Hyogo 6500047, Japan
[5] Tokai Univ, Sch Med, Dept Regenerat Med, Isehara, Kanagawa 2591193, Japan
关键词
Spinal cord injury; Blood; CD133; Expansion; Angiogenesis; Gliosis; Axon growth; ENDOTHELIAL PROGENITOR CELLS; FUNCTIONAL RECOVERY; REACTIVE ASTROCYTES; STEM-CELLS; VASCULAR NICHE; TIE2; RECEPTOR; CD34(+) CELLS; ADULT; ANGIOPOIETIN-1; GROWTH;
D O I
10.1016/j.jns.2013.02.013
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Human blood-derived CD133(+) cell populations, which are believed to represent a hematopoietic/endothelial progenitor fraction, have the ability to promote the repair of injured spinal cord in animal models. However, the mechanisms by which CD133(+) cell transplantation promotes spinal cord regeneration remain to be clarified. Another possible hurdle on the way to clinical applicability of these cells is their scarce representation in the overall population of mononuclear cells. We therefore analyzed and compared ex-vivo expanded human cord blood derived CD133(+) cells with freshly isolated CD133(+) cells as well as corresponding CD133(-) control mononuclear cells in respect to their ability to promote spinal cord repair using in vitro assays and cell transplantation into a mouse spinal cord injury model. In vitro, expanded cells as well as fresh CD133(+) cells formed endothelial progenitor cell (EPC) colonies, whereas CD133(-) cells formed no EPC colonies. In vivo, the administration of fresh CD133(+) and expanded cells enhanced angiogenesis, astrogliosis, axon growth and functional recovery after injury. In contrast, the administration of CD133(-) cells failed to promote axon growth and functional recovery, but moderately enhanced angiogenesis and astrogliosis. In addition, high-dose administration of expanded cells was highly effective in the induction of regenerative processes at the injured spinal cord. (c) 2013 Elsevier B.V. All rights reserved.
引用
收藏
页码:41 / 50
页数:10
相关论文
共 46 条
[1]   Tie2 receptor ligands, angiopoietin-1 and angiopoietin-2, modulate VEGF-induced postnatal neovascularization [J].
Asahara, T ;
Chen, DH ;
Takahashi, T ;
Fujikawa, K ;
Kearney, M ;
Magner, M ;
Yancopoulos, GD ;
Isner, JM .
CIRCULATION RESEARCH, 1998, 83 (03) :233-240
[2]   Isolation of putative progenitor endothelial cells for angiogenesis [J].
Asahara, T ;
Murohara, T ;
Sullivan, A ;
Silver, M ;
vanderZee, R ;
Li, T ;
Witzenbichler, B ;
Schatteman, G ;
Isner, JM .
SCIENCE, 1997, 275 (5302) :964-967
[3]   DIFFERENCES BETWEEN ADULT AND NEONATAL RATS IN THEIR ASTROGLIAL RESPONSE TO SPINAL-INJURY [J].
BARRETT, CP ;
DONATI, EJ ;
GUTH, L .
EXPERIMENTAL NEUROLOGY, 1984, 84 (02) :374-385
[4]   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
[5]   Skin-derived precursors generate myelinating Schwann cells that promote remyelination and functional recovery after contusion spinal cord injury [J].
Biernaskie, Jeff ;
Sparling, Joseph S. ;
Liu, Jie ;
Shannon, Casey P. ;
Plemel, Jason R. ;
Xie, Yuanyun ;
Miller, Freda D. ;
Tetzlaff, Wolfram .
JOURNAL OF NEUROSCIENCE, 2007, 27 (36) :9545-9559
[6]   Chondroitinase ABC promotes functional recovery after spinal cord injury [J].
Bradbury, EJ ;
Moon, LDF ;
Popat, RJ ;
King, VR ;
Bennett, GS ;
Patel, PN ;
Fawcett, JW ;
McMahon, SB .
NATURE, 2002, 416 (6881) :636-640
[7]   Leukocyte infiltration, neuronal degeneration, and neurite outgrowth after ablation of scar-forming, reactive astrocytes in adult transgenic mice [J].
Bush, TG ;
Puvanachandra, N ;
Horner, CH ;
Polito, A ;
Ostenfeld, T ;
Svendsen, CN ;
Mucke, L ;
Johnson, MH ;
Sofroniew, MV .
NEURON, 1999, 23 (02) :297-308
[8]   Interleukin 6 induces the expression of vascular endothelial growth factor [J].
Cohen, T ;
Nahari, D ;
Cerem, LW ;
Neufeld, G ;
Levi, BZ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (02) :736-741
[9]   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
[10]   TUMOR-NECROSIS-FACTOR TYPE-ALPHA, A POTENT INHIBITOR OF ENDOTHELIAL-CELL GROWTH-INVITRO, IS ANGIOGENIC INVIVO [J].
FRATERSCHRODER, M ;
RISAU, W ;
HALLMANN, R ;
GAUTSCHI, P ;
BOHLEN, P .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (15) :5277-5281