Neuroprotection by cord blood neural progenitors involves antioxidants, neurotrophic and angiogenic factors.
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.
Arien-Zakay
Hadar
H
Department of Pharmacology and Experimental Therapeutics, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Lecht
Shimon
S
Bercu
Marian M
MM
Tabakman
Rinat
R
Kohen
Ron
R
Galski
Hanan
H
Nagler
Arnon
A
Lazarovici
Philip
P
D042501:Angiogenic Proteins / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018920:Coculture Techniques; D019610:Cytoprotection / Q000502:physiology*; D005312:Fetal Blood / Q000166:cytology*; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology; D009414:Nerve Growth Factors / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology; D016716:PC12 Cells; D010641:Phenotype; D051381:Rats; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D020521:Stroke / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy
D042501:Angiogenic Proteins; D000975:Antioxidants; D005609:Free Radicals; D009414:Nerve Growth Factors