1. ¹Department of Pharmacology and Experimental Therapeutics, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
2. ²The Sheba Cancer Research Center, Chaim Sheba Medical Center, Tel-Hashomer, Israel
3. ³Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
4. ⁴Laboratory of Molecular Immunobiology, Division of Hematology and Bone Marrow Transplantation and Cord Blood Bank, Chaim Sheba Medical Center, Tel-Hashomer, Israel

Correspondence: Professor P Lazarovici, Department of Pharmacology and Experimental Therapeutics, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Ein Karem, POB 12065, Jerusalem 91120, Israel. E-mail: philipl@ekmd.huji.ac.il

⁵This study is part of a PhD thesis to be submitted to The Hebrew University of Jerusalem by HAZ

Received 1 April 2009; Accepted 15 April 2009; Published online 21 May 2009.

Abstract

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- (IFN-) contributes to HUCBNP differentiation. IFN- was detected in the CM used for the induction of differentiation of HUCBNP and a neutralizing antibody of IFN- significantly inhibited either IFN- 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--receptor signal transducer and activator of transcription) and chemokine C-X-C motif ligand 5). Treatment of HUCBNP with human recombinant IFN-, inhibited cell proliferation in a dose-dependent manner. IFN- (1–100 ng/ml) enhanced neuronal differentiation, expressed by neurite outgrowths and increased expression of the neuronal markers -tubulin III, microtubule-associated protein 2, neuronal nuclei, neurofilament M and neuronal-specific enolase. IFN- additively cooperated with NGF to induce the differentiation of HUCBNP. These data indicate that IFN- promotes neuronal differentiation of HUCB-derived progenitors, proposing its use in future protocols towards cell therapy.