Cord blood administration induces oligodendrocyte survival through alterations in gene expression.
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.
Rowe
D D
DD
Department of Molecular Pharmacology and Physiology, School of Basic Biomedical Sciences, College of Medicine, University of South Florida, Tampa, FL 33612, USA. drowe@health.usf.edu
Leonardo
C C
CC
Hall
A A
AA
Shahaduzzaman
M D
MD
Collier
L A
LA
Willing
A E
AE
Pennypacker
K R
KR
D000818:Animals; D000831:Animals, Newborn; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004195:Disease Models, Animal; D005312:Fetal Blood / Q000378:metabolism*; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000502:physiology*; D005947:Glucose / Q000172:deficiency; D006801:Humans; D000860:Hypoxia; D020244:Infarction, Middle Cerebral Artery / Q000628:therapy; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism; D019081:O Antigens / Q000378:metabolism; D009836:Oligodendroglia / Q000187:drug effects / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D053675:Versicans / Q000235:genetics / Q000378:metabolism
D047908:Intracellular Signaling Peptides and Proteins; D009185:Myelin Proteins; D019081:O Antigens; D053675:Versicans; D007770:L-Lactate Dehydrogenase; D005947:Glucose