Subventricular Zone-Derived Neural Progenitor Cells Migrate Along a Blood Vessel Scaffold Toward The Post-stroke Striatum

Authors

  • Takuro Kojima,

    1. Department of Developmental and Regenerative Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
    2. Department of Physiology, Keio University School of Medicine, Tokyo, Japan
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  • Yuki Hirota,

    1. Department of Developmental and Regenerative Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
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  • Masatsugu Ema,

    1. Department of Anatomy and Embryology, Institute of Basic Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan
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  • Satoru Takahashi,

    1. Department of Anatomy and Embryology, Institute of Basic Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan
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  • Ichiro Miyoshi,

    1. Department of Comparative and Experimental Medicine and Center for Animal Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
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  • Hideyuki Okano,

    1. Department of Physiology, Keio University School of Medicine, Tokyo, Japan
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  • Kazunobu Sawamoto

    Corresponding author
    1. Department of Developmental and Regenerative Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
    • Nagoya City University, Graduate School of Medical Sciences, Department of Developmental and Regenerative Biology, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan

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    • Telephone: 81-52-853-8532; Fax: 81-52-851-1898


  • Author contributions: T.K.: conception and design, collection and assembly of data, data analysis and interpretation, financial support, manuscript writing; Y.H.: conception and design, data analysis and interpretation, manuscript writing; M.E. and S.T.: provision of study material or patients, data analysis and interpretation; I.M.: provision of study material or patients; H.O.: conception and design, data analysis and interpretation, financial support, administrative support; K.S.: conception and design, data analysis and interpretation, financial support, manuscript writing.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • First published online in STEM CELLSEXPRESS January 13, 2010; available online without subscription through the open access option.

Abstract

The subventricular zone (SVZ) of the adult brain contains neural stem cells that have the capacity to regenerate new neurons after various insults. Brain ischemia causes damage to brain tissue and induces neural regeneration together with angiogenesis. We previously reported that, after ischemic injury in mice, SVZ-derived neural progenitor cells (NPCs) migrate into the striatum, and these NPCs are frequently associated with blood vessels in the regenerating brain tissue. Here we studied the role of blood vessels during the neural regeneration in more detail. BrdU administration experiments revealed that newly generated NPCs were associated with both newly formed and pre-existing blood vessels in the ischemic striatum, suggesting that the angiogenic environment is not essential for the neuron-blood vessel interaction. To observe migrating NPCs and blood vessels simultaneously in damaged brain tissue, we performed live imaging of cultured brain slices after ischemic injury. In this system, we virally labeled SVZ-derived NPCs in Flk1-EGFP knock-in mice in which the blood vessels are labeled with EGFP. Our results provide direct evidence that SVZ-derived NPCs migrate along blood vessels from the SVZ toward the ischemic region of the striatum. The leading process of the migrating NPCs was closely associated with blood vessels, suggesting that this interaction provides directional guidance to the NPCs. These findings suggest that blood vessels play an important role as a scaffold for NPCs migration toward the damaged brain region. STEM CELLS 2010;28:545–554

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