Anatomical and functional recovery by embryonic stem cell-derived neural tissue of a mouse model of brain damage

被引:34
作者
Chiba, S
Ikeda, R
Kurokawa, MS
Yoshikawa, H
Takeno, M
Nagafuchi, H
Tadokoro, M
Sekino, H
Hashimoto, T
Suzuki, N
机构
[1] St Marianna Univ, Dept Immunol, Sch Med, Kawasaki, Kanagawa 2168511, Japan
[2] St Marianna Univ, Dept Med, Sch Med, Kawasaki, Kanagawa 2168511, Japan
[3] St Marianna Univ, Sch Med, Dept Neurosurg, Kawasaki, Kanagawa, Japan
[4] St Marianna Univ, Sch Med, Dept Pathol, Kawasaki, Kanagawa, Japan
[5] St Marianna Univ, Grad Sch Med, Inst Adv Med Sci, Dept Regenerat Med, Kawasaki, Kanagawa, Japan
关键词
embryonic stem cell; hemiplegia; retinoic acid; motor function; neural cell; transplantation; recovery;
D O I
10.1016/j.jns.2004.01.006
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
We have treated undifferentiated mouse embryonic stem (ES) cells with all-trans retinoic acid (RA) to induce differentiation in vitro into neuron-like cells with good cell viability for use as a graft. Furthermore, we asked whether the RA-induced neuron-like cells restored neurological dysfunction. To this end, the cells were transplanted into right hemiplegia model of mice, developed by a cryogenic injury of motor cortex. Motor function of the recipients was gradually improved, whereas little improvement was observed in control mice. The lesion showed clustering of mature and almost mature neuron-like cells in mice transplanted with the RA-treated cells. The grafted cells had synaptic vesicles. This finding may suggest their maturation and synaptic connection in the recipient brain. Even though further study is necessary to elucidate molecular and cellular mechanisms responsible for the functional recovery, we consider that the ES cells may have advantage for use as a donor source in various neurological disorders including motor dysfunction. (C) 2004 Elsevier B.V. All rights reserved.
引用
收藏
页码:107 / 117
页数:11
相关论文
共 52 条
[1]
Conditioning effects of repetitive mild neurotrauma on motor function in an animal model of focal brain injury [J].
Allen, GV ;
Gerami, D ;
Esser, MJ .
NEUROSCIENCE, 2000, 99 (01) :93-105
[2]
Transplantation of fetal brain tissue into the site of intracerebral hemorrhage in rats [J].
Altumbabic, M ;
Del Bigio, MR .
NEUROSCIENCE LETTERS, 1998, 257 (02) :61-64
[3]
[Anonymous], MOUSE BRAINS COMP CY
[4]
Embryonic stem-cell derived neurones express a maturation dependent pattern of voltage-gated calcium channels and calcium-binding proteins [J].
Arnhold, S ;
Andressen, C ;
Angelov, DN ;
Vajna, R ;
Volsen, SG ;
Hescheler, J ;
Addicks, K .
INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE, 2000, 18 (2-3) :201-212
[5]
Retinoic acid promotes neural and represses mesodermal gene expression in mouse embryonic stem cells in culture [J].
Bain, G ;
Ray, WJ ;
Yao, M ;
Gottlieb, DI .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1996, 223 (03) :691-694
[6]
EMBRYONIC STEM-CELLS EXPRESS NEURONAL PROPERTIES IN-VITRO [J].
BAIN, G ;
KITCHENS, D ;
YAO, M ;
HUETTNER, JE ;
GOTTLIEB, DI .
DEVELOPMENTAL BIOLOGY, 1995, 168 (02) :342-357
[7]
Benninger Y, 2000, BRAIN PATHOL, V10, P330
[8]
Neuronal progenitors as tools for cell replacement in the nervous system [J].
Brustle, O ;
McKay, RDG .
CURRENT OPINION IN NEUROBIOLOGY, 1996, 6 (05) :688-695
[9]
Embryonic stem cell-derived glial precursors:: A source of myelinating transplants [J].
Brüstle, O ;
Jones, KN ;
Learish, RD ;
Karram, K ;
Choudhary, K ;
Wiestler, OD ;
Duncan, ID ;
McKay, RDG .
SCIENCE, 1999, 285 (5428) :754-756
[10]
Intracerebral transplantation of bone marrow with BDNF after MCAo in rat [J].
Chen, JL ;
Li, Y ;
Chopp, M .
NEUROPHARMACOLOGY, 2000, 39 (05) :711-716