Intraarterially delivered human umbilical cord blood-derived mesenchymal stem cells in canine cerebral ischemia

J Neurosci Res. 2009 Dec;87(16):3554-67. doi: 10.1002/jnr.22162.


The present study examined the effects of human umbilical cord blood-derived mesenchymal stem cells (HUCB-derived MSCs) delivered through the basilar artery in a canine thromboembolic brain ischemia model. Cerebral ischemia was induced through occlusion of the middle cerebral artery by injecting thrombus emboli into 10 beagles. In the HUCBC group (n = 5), 1 x 10(6) HUCB-derived MSCs were transplanted through the basilar artery 1 day after ischemic induction using an endovascular interventional approach. In the control group (n = 5), phosphate-buffered saline (PBS) was injected in the same manner in as the HUCBC group. Upon neurobehavioral examination, earlier recovery was observed in the HUCBC group. The HUCBC group showed a decrease in the infarction volume at 1 week after cerebral ischemic induction, whereas the control group showed an increase in the infarction volume at 1 week, by magnetic resonance image analysis. Transplanted cells had differentiated into neurons and astrocytes and were observed in and around endothelial cells that were positive for von Willebrand factor (vWF). HUCB-derived MSCs expressed neuroprotective factors, such as brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF), at 4 weeks after the transplantation. The transplanted cells demonstrated their efficacy by reducing the infarction lesion volume and through earlier recovery from the neurological deficit. These results suggest that intraarterial transplantation of HUCB-derived MSCs could be useful in clinical treatment of cerebral ischemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / metabolism
  • Astrocytes / pathology
  • Brain / metabolism
  • Brain / pathology*
  • Brain Ischemia / metabolism
  • Brain Ischemia / pathology*
  • Brain Ischemia / therapy*
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cell Differentiation / physiology
  • Cord Blood Stem Cell Transplantation
  • Dogs
  • Fluorescent Antibody Technique
  • Humans
  • Infarction, Middle Cerebral Artery / metabolism
  • Infarction, Middle Cerebral Artery / pathology
  • Infarction, Middle Cerebral Artery / therapy
  • Magnetic Resonance Imaging
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells
  • Neurons / metabolism
  • Neurons / pathology*
  • Recovery of Function
  • Statistics, Nonparametric
  • Time Factors
  • Transplantation, Heterologous
  • Vascular Endothelial Growth Factor A / metabolism
  • von Willebrand Factor / metabolism


  • Brain-Derived Neurotrophic Factor
  • Vascular Endothelial Growth Factor A
  • von Willebrand Factor