1. Cord blood administration induces oligodendrocyte survival through alterations in gene expression.
- Author
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Rowe DD, Leonardo CC, Hall AA, Shahaduzzaman MD, Collier LA, Willing AE, and Pennypacker KR
- Subjects
- Animals, Animals, Newborn, Cell Proliferation, Cell Survival physiology, Cell- and Tissue-Based Therapy methods, Cells, Cultured, Cerebral Cortex cytology, Disease Models, Animal, Gene Expression Profiling methods, Glucose deficiency, Humans, Hypoxia, Infarction, Middle Cerebral Artery therapy, Intracellular Signaling Peptides and Proteins genetics, Intracellular Signaling Peptides and Proteins metabolism, L-Lactate Dehydrogenase metabolism, Myelin Proteins genetics, Myelin Proteins metabolism, O Antigens metabolism, Oligodendroglia drug effects, Oligonucleotide Array Sequence Analysis methods, Rats, Rats, Sprague-Dawley, Time Factors, Versicans genetics, Versicans metabolism, Fetal Blood metabolism, Gene Expression Regulation physiology, Oligodendroglia physiology
- Abstract
Oligodendrocytes (OLs), the predominant cell type found in cerebral white matter, are essential for structural integrity and proper neural signaling. Very little is known concerning stroke-induced OL dysfunction. Our laboratory has shown that infusion of human umbilical cord blood (HUCB) cells protects striatal white matter tracts in vivo and directly protects mature primary OL cultures from oxygen glucose deprivation (OGD). Microarray studies of RNA prepared from OL cultures subjected to OGD and treated with HUCB cells showed an increase in the expression of 33 genes associated with OL proliferation, survival, and repair functions, such as myelination. The microarray results were verified using quantitative RT-PCR for the following eight genes: U2AF homology motif kinase 1 (Uhmk1), insulin-induced gene 1 (Insig1), metallothionein 3 (Mt3), tetraspanin 2 (Tspan2), peroxiredoxin 4 (Prdx4), stathmin-like 2 (Stmn2), myelin oligodendrocyte glycoprotein (MOG), and versican (Vcan). Immunohistochemistry showed that MOG, Prdx4, Uhmk1, Insig1, and Mt3 protein expression were upregulated in the ipsilateral white matter tracts of rats infused with HUCB cells 48h after middle cerebral artery occlusion (MCAO). Furthermore, promoter region analysis of these genes revealed common transcription factor binding sites, providing insight into the shared signal transduction pathways activated by HUCB cells to enhance transcription of these genes. These results show expression of genes induced by HUCB cell therapy that could confer oligoprotection from ischemia., (Copyright © 2010 Elsevier B.V. All rights reserved.)
- Published
- 2010
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