Transplanted hematopoietic stem cells from bone marrow differentiate into neural lineage cells and promote functional recovery after spinal cord injury in mice

被引:119
作者
Koshizuka, S
Okada, S
Okawa, A
Koda, M
Murasawa, M
Hashimoto, M
Kamada, T
Yoshinaga, K
Murakami, M
Moriya, H
Yamazaki, M
机构
[1] Chiba Univ, Grad Sch Med, Dept Orthopaed Surg, Chuo Ku, Chiba 2608670, Japan
[2] Kumamoto Univ, Div Hematopoiesis, Ctr AIDS Res, Kumamoto, Japan
[3] Chiba Univ Hosp, Div Rehabil Med, Chiba, Japan
关键词
bone marrow; hematopoietic stem cell; spinal cord injury; transplantation;
D O I
10.1093/jnen/63.1.64
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Recovery in central nervous system disorders is hindered by the limited ability of the vertebrate central nervous system to regenerate lost cells, replace damaged myelin, and re-establish functional neural connections. Cell transplantation to repair central nervous system disorders is an active area of research, with the goal of reducing functional deficits. Recent animal studies showed that cells of the hematopoietic stem cell (HSC) fraction of bone marrow transdifferentiated into various nonhematopoietic cell lineages. We employed a mouse model of spinal cord injury and directly transplanted HSCs into the spinal cord I week after injury. We evaluated functional recovery using the hindlimb motor function score weekly for 5 weeks after transplantation. The data demonstrated a significant improvement in the functional outcome of mice transplanted with hematopoietic stem cells compared with control mice in which only medium was injected. Fluorescent in situ hybridization for the Y chromosome and double immunohistochemistry showed that transplanted cells survived 5 weeks after transplantation and expressed specific markers for astrocytes, oligodendrocytes, and neural precursors, but not for neurons. These results suggest that transplantation of HSCs from bone marrow is an effective strategy for the treatment of spinal cord injury.
引用
收藏
页码:64 / 72
页数:9
相关论文
共 40 条
[1]   A SENSITIVE AND RELIABLE LOCOMOTOR RATING-SCALE FOR OPEN-FIELD TESTING IN RATS [J].
BASSO, DM ;
BEATTIE, MS ;
BRESNAHAN, JC .
JOURNAL OF NEUROTRAUMA, 1995, 12 (01) :1-21
[2]   Methylprednisolone and acute spinal cord injury - An update of the randomized evidence [J].
Bracken, MB .
SPINE, 2001, 26 (24) :S47-S54
[3]   From marrow to brain: Expression of neuronal phenotypes in adult mice [J].
Brazelton, TR ;
Rossi, FMV ;
Keshet, GI ;
Blau, HM .
SCIENCE, 2000, 290 (5497) :1775-1779
[4]   Pluripotent stem cells engrafted into the normal or lesioned adult rat spinal cord are restricted to a glial lineage [J].
Cao, QL ;
Zhang, YP ;
Howard, RM ;
Walters, WM ;
Tsoulfas, P ;
Whittemore, SR .
EXPERIMENTAL NEUROLOGY, 2001, 167 (01) :48-58
[5]   Differentiation of engrafted neuronal-restricted precursor cells is inhibited in the traumatically injured spinal cord [J].
Cao, QL ;
Howard, RM ;
Dennison, JB ;
Whittemore, SR .
EXPERIMENTAL NEUROLOGY, 2002, 177 (02) :349-359
[6]   Therapeutic benefit of intracerebral transplantation of bone marrow stromal cells after cerebral ischemia in rats [J].
Chen, JL ;
Li, Y ;
Wang, L ;
Lu, M ;
Zhang, XH ;
Chopp, M .
JOURNAL OF THE NEUROLOGICAL SCIENCES, 2001, 189 (1-2) :49-57
[7]   Spinal cord injury in rat: treatment with bone marrow stromal cell transplantation [J].
Chopp, M ;
Zhang, XH ;
Li, Y ;
Wang, L ;
Chen, JL ;
Lu, DY ;
Lu, M ;
Rosenblum, M .
NEUROREPORT, 2000, 11 (13) :3001-3005
[8]   Neuroectodermal and microglial differentiation of bone marrow cells in the mouse spinal cord and sensory ganglia [J].
Corti, S ;
Locatelli, F ;
Donadoni, C ;
Strazzer, S ;
Salani, S ;
Del Bo, R ;
Caccialanza, M ;
Bresolin, N ;
Scarlato, G ;
Comi, GP .
JOURNAL OF NEUROSCIENCE RESEARCH, 2002, 70 (06) :721-733
[9]   ACCESSIBILITY OF DNA INSITU TO VARIOUS FLUOROCHROMES - RELATIONSHIP TO CHROMATIN CHANGES DURING ERYTHROID-DIFFERENTIATION OF FRIEND-LEUKEMIA CELLS [J].
DARZYNKIEWICZ, Z ;
TRAGANOS, F ;
KAPUSCINSKI, J ;
STAIANOCOICO, L ;
MELAMED, MR .
CYTOMETRY, 1984, 5 (04) :355-363
[10]   Hematopoietic cells differentiate into both microglia and macroglia in the brains of adult mice [J].
Eglitis, MA ;
Mezey, E .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (08) :4080-4085