Therapeutic benefits of human mesenchymal stem cells derived from bone marrow after global cerebral ischemia

Brain Res. 2010 Jan 15:1310:8-16. doi: 10.1016/j.brainres.2009.11.012. Epub 2009 Nov 12.

Abstract

Although intravenous delivery of mesenchymal stem cells (MSCs) prepared from adult bone marrow reduces infarction size and ameliorates functional deficits in rat middle cerebral artery occlusion models, there are few reports of MSC treatment in global cerebral ischemia. We utilized a global cerebral ischemia model induced by arresting the heart with a combination of hypovolemia and intracardiac injections of a cold potassium chloride solution in order to study the potential therapeutic benefits of human mesenchymal stem cells (hMSCs) on global cerebral ischemia. hMSCs were intravenously injected into the rats 3 h after resuscitation from cardiac arrest. The effects on structural and functional outcome of hMSC were assessed at 5 h and 1, 3, and 7 days using magnetic resonance spectroscopy (MRS), histology, and cognitive functional analysis. Intravenous delivery of hMSCs reduced the Lac/Cr ratios, nuclear DNA fragmentation, neuronal loss, and elicited functional improvement compared with the control sham group. Enzyme-linked immunosorbent assay (ELISA) of the hippocampus revealed an increase in BDNF in hMSC-treated group. These data suggest that intravenous delivery of hMSC may have a therapeutic effect in global cerebral ischemia.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Analysis of Variance
  • Animals
  • Bone Marrow Cells / physiology*
  • Brain Ischemia / complications
  • Brain Ischemia / surgery*
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cell Count / methods
  • Creatine / metabolism
  • Disease Models, Animal
  • Heart Arrest / etiology
  • Heart Arrest / therapy
  • Humans
  • In Situ Nick-End Labeling / methods
  • Lactic Acid / metabolism
  • Magnetic Resonance Imaging / methods
  • Male
  • Maze Learning / physiology
  • Mesenchymal Stem Cell Transplantation / methods*
  • Rats
  • Rats, Wistar
  • Time Factors

Substances

  • Brain-Derived Neurotrophic Factor
  • Lactic Acid
  • Creatine