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The great migration of bone marrow-derived stem cells toward the ischemic brain: therapeutic implications for stroke and other neurological disorders
Authors:Borlongan Cesar V  Glover Loren E  Tajiri Naoki  Kaneko Yuji  Freeman Thomas B
Institution:Department of Neurosurgery and Brain Repair, University of South Florida College of Medicine, 12901 Bruce B. Downs Blvd, Tampa, FL 33612, USA. cborlong@health.usf.edu
Abstract:Accumulating laboratory studies have implicated the mobilization of bone marrow (BM)-derived stem cells in brain plasticity and stroke therapy. This mobilization of bone cells to the brain is an essential concept in regenerative medicine. Over the past ten years, mounting data have shown the ability of bone marrow-derived stem cells to mobilize from BM to the peripheral blood (PB) and eventually enter the injured brain. This homing action is exemplified in BM stem cell mobilization following ischemic brain injury. Various BM-derived cells, such as hematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs), endothelial progenitor cells (EPCs) and very small embryonic-like cells (VSELs) have been demonstrated to exert therapeutic benefits in stroke. Here, we discuss the current status of these BM-derived stem cells in stroke therapy, with emphasis on possible cellular and molecular mechanisms of action that mediate the cells' beneficial effects in the ischemic brain. When possible, we also discuss the relevance of this therapeutic regimen in other central nervous system (CNS) disorders.
Keywords:BM  bone marrow  PB  peripheral blood  HSCs  hematopoietic stem cells  MSCs  mesenchymal stem cells  EPCs  endothelial progenitor stem cells  VSELs  very small embryonic-like stem cells  BBB  blood brain barrier  SDF-1  stromal derived factor-1  CNS  central nervous system  G-CSF  granulocyte-colony stimulating factor  GM-CSF  granulocyte-macrophage colony stimulating factor  CB  cord blood  HGF  hepatocyte growth factor  VEGF  vascular endothelial growth factor  NGF  nerve growth factor  BDNF  brain-derived neurotrophic factor  bFGF  basic fibroblast growth factor  VEGFR2  vascular endothelial growth factor receptor 2  IGF-1  insulin growth factor-1  IBZ  ischemia border zone  SVZ  subventricular zone  SGZ  subgranular zone  MCAo  middle cerebral artery occlusion  GDNF  glial cell line-derived neurotrophic factor  CNTF  ciliary neurotrophic factor  NT3  neurotrophin-3  Cx43  connexin-43  UCB  umbilical cord blood  PSC  progenitor stem cells
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