Neuroprotection by cord blood neural progenitors involves antioxidants, neurotrophic and angiogenic factors

Exp Neurol. 2009 Mar;216(1):83-94. doi: 10.1016/j.expneurol.2008.11.006. Epub 2008 Nov 25.

Abstract

Human umbilical cord blood (HUCB) is a valuable source for cell therapy since it confers neuroprotection in stroke animal models. However, the responsible sub-populations remain to be established and the mechanisms involved are unknown. To explore HUCB neuroprotective properties in a PC12 cell-based ischemic neuronal model, we used an HUCB mononuclear-enriched population of collagen-adherent cells, which can be differentiated in vitro into a neuronal phenotype (HUCBNP). Upon co-culture with insulted-PC12 cells, HUCBNP conferred approximately 30% neuroprotection, as evaluated by decreased lactate dehydrogenase and caspase-3 activities. HUCBNP decreased by 95% the level of free radicals in the insulted-PC12 cells, in correlation with the appearance of antioxidants, as measured by changes in the oxidation-reduction potential of the medium using cyclic-voltammetry. An increased level of nerve growth factor (NGF), vascular endothelial growth factor and basic fibroblast growth factor in the co-culture medium was temporally correlated with a -medium neuroprotection effect, which was partially abolished by heat denaturation. HUCBNP-induced neuroprotection was correlated with changes in gene expression of these neurotrophic factors, while blocked by K252a, an antagonist of the TrkA/NGF receptor. These findings indicate that HUCBNP-induced neuroprotection involves antioxidant(s) and neurotrophic factors, which, by paracrine and/or autocrine interactions between the insulted-PC12 and the HUCBNP cells, conferred neuroprotection.

MeSH terms

  • Angiogenic Proteins / metabolism*
  • Animals
  • Antioxidants / metabolism*
  • Cell Differentiation / physiology
  • Cell Line, Tumor
  • Cells, Cultured
  • Coculture Techniques
  • Cytoprotection / physiology*
  • Fetal Blood / cytology*
  • Free Radicals / metabolism
  • Humans
  • Hypoxia-Ischemia, Brain / metabolism
  • Hypoxia-Ischemia, Brain / physiopathology
  • Hypoxia-Ischemia, Brain / therapy
  • Neovascularization, Physiologic / drug effects
  • Neovascularization, Physiologic / physiology
  • Nerve Growth Factors / metabolism*
  • Neurons / metabolism*
  • Oxidation-Reduction
  • Oxidative Stress / physiology
  • PC12 Cells
  • Phenotype
  • Rats
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Stroke / metabolism
  • Stroke / physiopathology
  • Stroke / therapy

Substances

  • Angiogenic Proteins
  • Antioxidants
  • Free Radicals
  • Nerve Growth Factors