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TISSUE-SPECIFIC STEM CELLS |
aDepartment of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA;
bDepartment of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA;
cDepartment of Pharmacology and Toxicology, University of Kansas, Lawrence, Kansas, USA
Key Words. Cerebral global ischemia • Rat umbilical cord matrix cell • Oct-4 • Extracellular signaling • Neurogenesis • Reperfusion Stem cell therapy
Correspondence: Yan Xu, Ph.D., University of Pittsburgh School of Medicine, Biomedical Science Tower 3, Room 2048, 3501 Fifth Avenue, Pittsburgh, Pennsylvania 15260, USA. Telephone: 412-648-9922; Fax: 412-648-8998; e-mail: xuy{at}anes.upmc.edu
Received on January 26, 2006;
accepted for publication on August 29, 2006.
First published online in STEM CELLS EXPRESS September 7, 2006.
Potential therapeutic effects of Oct-4-positive rat umbilical cord matrix (RUCM) cells in treating cerebral global ischemia were evaluated using a reproducible model of cardiac arrest (CA) and resuscitation in rats. Animals were randomly assigned to four groups: A, sham-operated; B, 8-minute CA without pretreatment; C, 8-minute CA pretreated with defined media; and D, 8-minute CA pretreated with Oct-4+ RUCM cells. Pretreatment was done 3 days before CA by 2.5-µl microinjection of defined media or approximately 104 Oct-4+ RUCM cells in left thalamic nucleus, hippocampus, corpus callosum, and cortex. Damage was assessed histologically 7 days after CA and was quantified by the percentage of injured neurons in hippocampal CA1 regions. Little damage (approximately 3%4%) was found in the sham group, whereas 50%68% CA1 pyramidal neurons were injured in groups B and C. Pretreatment with Oct-4+ RUCM cells significantly (p < .001) reduced neuronal loss to 25%32%. Although the transplanted cells were found to have survived in the brain with significant migration, few were found directly in CA1. Therefore, transdifferentiation and fusion with host cells cannot be the predominant mechanisms for the observed protection. The Oct-4+ RUCM cells might repair nonfocal tissue damage by an extracellular signaling mechanism. Treating cerebral global ischemia with umbilical cord matrix cells seems promising and worthy of further investigation.
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