Committed neural progenitor cells derived from genetically modified bone marrow stromal cells ameliorate deficits in a rat model of stroke

Makoto Hayase, Masaaki Kitada, Shohei Wakao, Yutaka Itokazu, Kazuhiko Nozaki, Nobuo Hashimoto, Yasushi Takagi, Mari Dezawa

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

Bone marrow stromal cells (MSCs) are an excellent source of cells for treating a variety of central nervous system diseases. In this study, we report the efficient induction of committed neural progenitor cells from rat and human MSCs (NS-MSCs) by introduction of cells with the intracellular domain of Notch-1 followed by growth in the free-floating culture system. NS-MSCs successfully formed spheres, in which cells highly expressed the neural precursor cell markers. The commitment of spheres to neural lineage cells was confirmed by their successful differentiation into neuronal cells when exposed to a differentiation medium. To determine the therapeutic potential of NS-MSCs, cells were transplanted into the cortex and striatum in a rat model of focal cerebral ischemia. The survival, distribution, and integration of NS-MSCs in the host brain were very high, and at day 100, grafted NS-MSCs were positive for dopaminergic, glutamatergic, and γ-amino butyric acid(GABA)ergic neuronal markers. They extended long neurites for nearly 6.3 mm and many of these expressed synaptophysin. Significant behavioral recovery was also observed in limb-placing and water-maze tests. These suggest a high potential for this MSC approach in the replenishment of neural cells for stroke and for a wide range of neurodegenerative conditions that require various types of neural cells.

Original languageEnglish (US)
Pages (from-to)1409-1420
Number of pages12
JournalJournal of Cerebral Blood Flow and Metabolism
Volume29
Issue number8
DOIs
StatePublished - Aug 1 2009
Externally publishedYes

Fingerprint

Mesenchymal Stromal Cells
Stromal Cells
Stem Cells
Stroke
Bone Marrow
Synaptophysin
Butyric Acid
Central Nervous System Diseases
Neurites
Brain Ischemia
Extremities
Survival
Water
Brain
Growth

Keywords

  • Bone marrow stromal cells
  • Cell therapy
  • Cerebral ischemia
  • Neuroprogenitors
  • Neurospheres
  • Transplantation

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Cite this

Committed neural progenitor cells derived from genetically modified bone marrow stromal cells ameliorate deficits in a rat model of stroke. / Hayase, Makoto; Kitada, Masaaki; Wakao, Shohei; Itokazu, Yutaka; Nozaki, Kazuhiko; Hashimoto, Nobuo; Takagi, Yasushi; Dezawa, Mari.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 29, No. 8, 01.08.2009, p. 1409-1420.

Research output: Contribution to journalArticle

Hayase, Makoto ; Kitada, Masaaki ; Wakao, Shohei ; Itokazu, Yutaka ; Nozaki, Kazuhiko ; Hashimoto, Nobuo ; Takagi, Yasushi ; Dezawa, Mari. / Committed neural progenitor cells derived from genetically modified bone marrow stromal cells ameliorate deficits in a rat model of stroke. In: Journal of Cerebral Blood Flow and Metabolism. 2009 ; Vol. 29, No. 8. pp. 1409-1420.
@article{e480abd2fa7d46bfa9dc23ae8c38ce7d,
title = "Committed neural progenitor cells derived from genetically modified bone marrow stromal cells ameliorate deficits in a rat model of stroke",
abstract = "Bone marrow stromal cells (MSCs) are an excellent source of cells for treating a variety of central nervous system diseases. In this study, we report the efficient induction of committed neural progenitor cells from rat and human MSCs (NS-MSCs) by introduction of cells with the intracellular domain of Notch-1 followed by growth in the free-floating culture system. NS-MSCs successfully formed spheres, in which cells highly expressed the neural precursor cell markers. The commitment of spheres to neural lineage cells was confirmed by their successful differentiation into neuronal cells when exposed to a differentiation medium. To determine the therapeutic potential of NS-MSCs, cells were transplanted into the cortex and striatum in a rat model of focal cerebral ischemia. The survival, distribution, and integration of NS-MSCs in the host brain were very high, and at day 100, grafted NS-MSCs were positive for dopaminergic, glutamatergic, and γ-amino butyric acid(GABA)ergic neuronal markers. They extended long neurites for nearly 6.3 mm and many of these expressed synaptophysin. Significant behavioral recovery was also observed in limb-placing and water-maze tests. These suggest a high potential for this MSC approach in the replenishment of neural cells for stroke and for a wide range of neurodegenerative conditions that require various types of neural cells.",
keywords = "Bone marrow stromal cells, Cell therapy, Cerebral ischemia, Neuroprogenitors, Neurospheres, Transplantation",
author = "Makoto Hayase and Masaaki Kitada and Shohei Wakao and Yutaka Itokazu and Kazuhiko Nozaki and Nobuo Hashimoto and Yasushi Takagi and Mari Dezawa",
year = "2009",
month = "8",
day = "1",
doi = "10.1038/jcbfm.2009.62",
language = "English (US)",
volume = "29",
pages = "1409--1420",
journal = "Journal of Cerebral Blood Flow and Metabolism",
issn = "0271-678X",
publisher = "Nature Publishing Group",
number = "8",

}

TY - JOUR

T1 - Committed neural progenitor cells derived from genetically modified bone marrow stromal cells ameliorate deficits in a rat model of stroke

AU - Hayase, Makoto

AU - Kitada, Masaaki

AU - Wakao, Shohei

AU - Itokazu, Yutaka

AU - Nozaki, Kazuhiko

AU - Hashimoto, Nobuo

AU - Takagi, Yasushi

AU - Dezawa, Mari

PY - 2009/8/1

Y1 - 2009/8/1

N2 - Bone marrow stromal cells (MSCs) are an excellent source of cells for treating a variety of central nervous system diseases. In this study, we report the efficient induction of committed neural progenitor cells from rat and human MSCs (NS-MSCs) by introduction of cells with the intracellular domain of Notch-1 followed by growth in the free-floating culture system. NS-MSCs successfully formed spheres, in which cells highly expressed the neural precursor cell markers. The commitment of spheres to neural lineage cells was confirmed by their successful differentiation into neuronal cells when exposed to a differentiation medium. To determine the therapeutic potential of NS-MSCs, cells were transplanted into the cortex and striatum in a rat model of focal cerebral ischemia. The survival, distribution, and integration of NS-MSCs in the host brain were very high, and at day 100, grafted NS-MSCs were positive for dopaminergic, glutamatergic, and γ-amino butyric acid(GABA)ergic neuronal markers. They extended long neurites for nearly 6.3 mm and many of these expressed synaptophysin. Significant behavioral recovery was also observed in limb-placing and water-maze tests. These suggest a high potential for this MSC approach in the replenishment of neural cells for stroke and for a wide range of neurodegenerative conditions that require various types of neural cells.

AB - Bone marrow stromal cells (MSCs) are an excellent source of cells for treating a variety of central nervous system diseases. In this study, we report the efficient induction of committed neural progenitor cells from rat and human MSCs (NS-MSCs) by introduction of cells with the intracellular domain of Notch-1 followed by growth in the free-floating culture system. NS-MSCs successfully formed spheres, in which cells highly expressed the neural precursor cell markers. The commitment of spheres to neural lineage cells was confirmed by their successful differentiation into neuronal cells when exposed to a differentiation medium. To determine the therapeutic potential of NS-MSCs, cells were transplanted into the cortex and striatum in a rat model of focal cerebral ischemia. The survival, distribution, and integration of NS-MSCs in the host brain were very high, and at day 100, grafted NS-MSCs were positive for dopaminergic, glutamatergic, and γ-amino butyric acid(GABA)ergic neuronal markers. They extended long neurites for nearly 6.3 mm and many of these expressed synaptophysin. Significant behavioral recovery was also observed in limb-placing and water-maze tests. These suggest a high potential for this MSC approach in the replenishment of neural cells for stroke and for a wide range of neurodegenerative conditions that require various types of neural cells.

KW - Bone marrow stromal cells

KW - Cell therapy

KW - Cerebral ischemia

KW - Neuroprogenitors

KW - Neurospheres

KW - Transplantation

UR - http://www.scopus.com/inward/record.url?scp=68249088090&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=68249088090&partnerID=8YFLogxK

U2 - 10.1038/jcbfm.2009.62

DO - 10.1038/jcbfm.2009.62

M3 - Article

C2 - 19436312

AN - SCOPUS:68249088090

VL - 29

SP - 1409

EP - 1420

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

SN - 0271-678X

IS - 8

ER -