Interferon-γ-induced neuronal differentiation of human umbilical cord blood-derived progenitors

• Published in: Leukemia Vol. 23; no. 10; pp. 1790 - 1800
• Main Authors: Arien-Zakay, H, Lecht, S, Bercu, M M, Amariglio, N, Rechavi, G, Galski, H, Lazarovici, P, Nagler, A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.10.2009; Nature Publishing Group
• Subjects: 2',5'-Oligoadenylate Synthetase - genetics; 2',5'-Oligoadenylate Synthetase - metabolism; Antibodies; Antineoplastic Agents - pharmacology; Biological and medical sciences; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Blood; Blotting, Western; Cancer Research; Cell differentiation; Cell Differentiation - drug effects; Cell proliferation; Cell Proliferation - drug effects; Cell therapy; Cells, Cultured; Cellular therapy; Chemokines; Cord blood; Critical Care Medicine; Culture Media, Conditioned - pharmacology; Degeneration; Differentiation; Enzyme-Linked Immunosorbent Assay; Fetal blood; Fetal Blood - cytology; Fetal Blood - drug effects; Fetal Blood - metabolism; Gene Expression Profiling; Genetic aspects; Growth factors; Health aspects; Hematologic and hematopoietic diseases; Hematology; Hemopoiesis; Humans; Hypoxia; Immunoenzyme Techniques; Intensive; Interferon; Interferon gamma; Interferon-gamma - pharmacology; Internal Medicine; Medical sciences; Medicine; Medicine & Public Health; Membrane proteins; Microtubule-associated protein 2; Nerve growth factor; Nervous system; Neural stem cells; Neuroblastoma; Neuroblastoma - drug therapy; Neuroblastoma - metabolism; Neuroblastoma - pathology; Neurons - cytology; Neurons - drug effects; Neurons - metabolism; Neuroprotection; Oligonucleotide Array Sequence Analysis; Oncology; original-article; Phenotypes; Phosphopyruvate hydratase; Progenitor cells; Proteins; Recombinant Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Messenger - metabolism; Stat1 protein; STAT1 Transcription Factor - genetics; STAT1 Transcription Factor - metabolism; Stem Cells - drug effects; Stem Cells - metabolism; Transcription; Transcriptomes; Tubulin; Umbilical cord; γ-Interferon; Israel; IFN-γ; human umbilical cord blood; NGF; neuronal differentiation; gene expression; neuronal progenitors; Human; Hematology; Stem cell; Nerve growth factor; Cell differentiation; Gene expression; Blood; Neuron; Umbilical cord; Gamma interferon
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/leu.2009.106

Human umbilical cord blood (HUCB) provides a source of progenitors for cell therapy. We isolated and characterized an HUCB-derived population of progenitors (HUCBNP), differentiated toward neuronal phenotype by human neuroblastoma-conditioning medium (CM) and nerve growth factor (NGF), which have been found to confer neuroprotection toward hypoxia-mediated neuronal injury. This study investigated whether interferon-γ (IFN-γ) contributes to HUCBNP differentiation. IFN-γ was detected in the CM used for the induction of differentiation of HUCBNP and a neutralizing antibody of IFN-γ significantly inhibited either IFN-γ or CM-induced differentiation. Transcriptome analysis of CM-differentiated HUCBNP, identified 86 genes as highly upregulated, among them 25 were IFN-induced (such as 2′,5′-oligoadenylate synthetase 1 and 2, IFN-induced protein and transmembrane proteins, STAT1 (IFN-γ-receptor signal transducer and activator of transcription) and chemokine C-X-C motif ligand 5). Treatment of HUCBNP with human recombinant IFN-γ, inhibited cell proliferation in a dose-dependent manner. IFN-γ (1–100 ng/ml) enhanced neuronal differentiation, expressed by neurite outgrowths and increased expression of the neuronal markers β-tubulin III, microtubule-associated protein 2, neuronal nuclei, neurofilament M and neuronal-specific enolase. IFN-γ additively cooperated with NGF to induce the differentiation of HUCBNP. These data indicate that IFN-γ promotes neuronal differentiation of HUCB-derived progenitors, proposing its use in future protocols towards cell therapy.