Acute injury directs the migration, proliferation, and differentiation of solid organ stem cells: Evidence from the effect of hypoxia-ischemia in the CNS on clonal "reporter" neural stem cells

被引:111
作者
Park, Kook In
Hack, Michael A.
Ourednik, Jitka
Yandava, Booma
Flax, Jonathan D.
Stieg, Philip E.
Gullans, Stephen
Jensen, Francis E.
Sidman, Richard L.
Ourednik, Vaclav
Snyder, Evan Y. [1 ]
机构
[1] Burnham Inst Med Res, Program Stem Cells & Regenerat, La Jolla, CA 92037 USA
[2] Yonsei Univ, Coll Med, Dept Pediat, Seoul 120749, South Korea
[3] Yonsei Univ, Coll Med, Brain Korea Project Med Sci 21, Seoul 120749, South Korea
[4] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA
[5] Iowa State Univ, Ames, IA USA
[6] Cornell Univ, Weill Sch Med, Dept Neurosurg, New York, NY USA
关键词
neural stem cells; neural injury and degeneration; stroke; transplantation; gene expression; development; reporter cells;
D O I
10.1016/j.expneurol.2006.04.002
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Clonal neural cells with stem-like features integrate appropriately into the developing and degenerating central and peripheral nervous system throughout the neuraxis. In response to hypoxic-ischemic (HI) injury, previously engrafted, integrated, and quiescent clonal neural stem cells (NSCs) transiently re-enter the cell cycle, migrate preferentially to the site of ischemia, and differentiate into neurons and oligodendrocytes, the neural cell types typically lost following HI brain injury. They also replenish the supply of immature uncommitted resident stem/progenitor cells. Although they yield astrocytes, scarring is inhibited. These responses appear to occur most robustly within a 3-7 day "window" following HI during which signals are elaborated that upregulate genetic programs within the NSC that mediate proliferation, migration, survival, and differentiation, most of which appear to be terminated once the "window closes" and the chronic phase ensues, sending the NSCs into a quiescent state. These insights derived from using the stem cell in a novel role-as a "reporter" cell-to both track and probe the activity of endogenous stem cells as well as to "interrogate" and "report" the genes differentially induced by the acutely vs. chronically injured milieu. NSCs may be capable of the replacement of cells, genes, and non-diffusible factors in both a widespread or more circumscribed manner (depending on the therapeutic demands of the clinical situation). They may be uniquely responsive to some types of neurodegenerative conditions. We submit that these various capabilities are simply the normal expression of the basic homeostasis-preserving biologic proper-ties and attributes of a stem cell which, if used rationally and in concert with this biology, may be exploited for therapeutic ends. (c) 2006 Elsevier Inc. All rights reserved.
引用
收藏
页码:156 / 178
页数:23
相关论文
共 76 条
[1]   Neural stem cells display extensive tropism for pathology in adult brain: Evidence from intracranial gliomas [J].
Aboody, KS ;
Brown, A ;
Rainov, NG ;
Bower, KA ;
Liu, SX ;
Yang, W ;
Small, JE ;
Herrlinger, U ;
Ourednik, V ;
Black, PM ;
Breakefield, XO ;
Snyder, EY .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (23) :12846-12851
[2]   Can stem cells cross lineage boundaries? [J].
Anderson, DJ ;
Gage, FH ;
Weissman, IL .
NATURE MEDICINE, 2001, 7 (04) :393-395
[3]   BCL-2 transduction, using a herpes simplex virus amplicon, protects hippocampal neurons from transient global ischemia [J].
Antonawich, FJ ;
Federoff, HJ ;
Davis, JN .
EXPERIMENTAL NEUROLOGY, 1999, 156 (01) :130-137
[4]   Neuronal replacement from endogenous precursors in the adult brain after stroke [J].
Arvidsson, A ;
Collin, T ;
Kirik, D ;
Kokaia, Z ;
Lindvall, O .
NATURE MEDICINE, 2002, 8 (09) :963-970
[5]   Developmental stage determines the effects of MYC in the mammary epithelium [J].
Blakely, CM ;
Sintasath, L ;
D'Cruz, CM ;
Hahn, KT ;
Dugan, KD ;
Belka, GK ;
Chodosh, LA .
DEVELOPMENT, 2005, 132 (05) :1147-1160
[6]   LIF/STAT3 controls ES cell self-renewal and pluripotency by a Myc-dependent mechanism [J].
Cartwright, P ;
McLean, C ;
Sheppard, A ;
Rivett, D ;
Jones, K ;
Dalton, S .
DEVELOPMENT, 2005, 132 (05) :885-896
[7]   Activation of apoptosis signal regulating kinase 1 (ASK1) by the adapter protein Daxx [J].
Chang, HY ;
Nishitoh, H ;
Yang, XL ;
Ichijo, H ;
Baltimore, D .
SCIENCE, 1998, 281 (5384) :1860-1863
[8]   Bcl-2 promotes regeneration of severed axons in mammalian CNS [J].
Chen, DF ;
Schneider, GE ;
Martinou, JC ;
Tonegawa, S .
NATURE, 1997, 385 (6615) :434-439
[9]  
CHEN SC, 1995, CELL GROWTH DIFFER, V6, P681
[10]   A transforming p53 mutant, which binds DNA, transactivates and induces apoptosis reveals a nuclear:cytoplasmic shuttling defect [J].
Crook, T ;
Parker, GA ;
Rozycka, M ;
Crossland, S ;
Allday, MJ .
ONCOGENE, 1998, 16 (11) :1429-1441