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

• Published in: Experimental neurology 2009-03, Vol.216 (1), p.83-94
• Main Authors: Arien-Zakay, Hadar, Lecht, Shimon, Bercu, Marian M., Tabakman, Rinat, Kohen, Ron, Galski, Hanan, Nagler, Arnon, Lazarovici, Philip
• Format: Article
• Language: English
• Subjects: Angiogenic Proteins - metabolism; Angiogenic Proteins - secretion; Animals; Antioxidants - metabolism; Biological and medical sciences; Cell Differentiation - physiology; Cell Line, Tumor; Cells, Cultured; Coculture Techniques; Cord blood progenitors; Cytoprotection - physiology; Fetal Blood - cytology; FGF-2; Free radicals; Free Radicals - metabolism; Humans; Hypoxia-Ischemia, Brain - metabolism; Hypoxia-Ischemia, Brain - physiopathology; Hypoxia-Ischemia, Brain - therapy; Injuries of the nervous system and the skull. Diseases due to physical agents; Medical sciences; Neovascularization, Physiologic - drug effects; Neovascularization, Physiologic - physiology; Nerve Growth Factors - metabolism; Nerve Growth Factors - secretion; Neurology; Neurons - metabolism; Neuroprotection; NGF; Oxidation-Reduction; Oxidative Stress - physiology; Oxygen–glucose deprivation; PC12 Cells; Phenotype; Rats; Stem Cells - cytology; Stem Cells - metabolism; Stem Cells - secretion; Stroke - metabolism; Stroke - physiopathology; Stroke - therapy; Traumas. Diseases due to physical agents; VEGF
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2008.11.006

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 ∼ 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.