Document Detail


Interferon-gamma-induced neuronal differentiation of human umbilical cord blood-derived progenitors.
MedLine Citation:
PMID:  19458627     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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-gamma (IFN-gamma) contributes to HUCBNP differentiation. IFN-gamma was detected in the CM used for the induction of differentiation of HUCBNP and a neutralizing antibody of IFN-gamma significantly inhibited either IFN-gamma 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-gamma-receptor signal transducer and activator of transcription) and chemokine C-X-C motif ligand 5). Treatment of HUCBNP with human recombinant IFN-gamma, inhibited cell proliferation in a dose-dependent manner. IFN-gamma (1-100 ng/ml) enhanced neuronal differentiation, expressed by neurite outgrowths and increased expression of the neuronal markers beta-tubulin III, microtubule-associated protein 2, neuronal nuclei, neurofilament M and neuronal-specific enolase. IFN-gamma additively cooperated with NGF to induce the differentiation of HUCBNP. These data indicate that IFN-gamma promotes neuronal differentiation of HUCB-derived progenitors, proposing its use in future protocols towards cell therapy.
Authors:
H Arien-Zakay; S Lecht; M M Bercu; N Amariglio; G Rechavi; H Galski; P Lazarovici; A Nagler
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-05-21
Journal Detail:
Title:  Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K     Volume:  23     ISSN:  1476-5551     ISO Abbreviation:  Leukemia     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-10-14     Completed Date:  2009-11-05     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8704895     Medline TA:  Leukemia     Country:  England    
Other Details:
Languages:  eng     Pagination:  1790-800     Citation Subset:  IM    
Affiliation:
Department of Pharmacology and Experimental Therapeutics, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.
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MeSH Terms
Descriptor/Qualifier:
2',5'-Oligoadenylate Synthetase / genetics,  metabolism
Antineoplastic Agents / pharmacology*
Blotting, Western
Cell Differentiation / drug effects*
Cell Proliferation / drug effects
Cells, Cultured
Culture Media, Conditioned / pharmacology
Enzyme-Linked Immunosorbent Assay
Fetal Blood / cytology,  drug effects*,  metabolism
Gene Expression Profiling
Humans
Immunoenzyme Techniques
Interferon-gamma, Recombinant / pharmacology*
Neuroblastoma / drug therapy,  metabolism,  pathology
Neurons / cytology,  drug effects*,  metabolism
Oligonucleotide Array Sequence Analysis
RNA, Messenger / genetics,  metabolism
Reverse Transcriptase Polymerase Chain Reaction
STAT1 Transcription Factor / genetics,  metabolism
Stem Cells / drug effects*,  metabolism
Tumor Markers, Biological / genetics,  metabolism
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Culture Media, Conditioned; 0/Interferon-gamma, Recombinant; 0/RNA, Messenger; 0/STAT1 Transcription Factor; 0/STAT1 protein, human; 0/Tumor Markers, Biological; EC 2.7.7.-/2',5'-Oligoadenylate Synthetase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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