Potential Treatment of Cerebral Global Ischemia with Oct-4⁺ Umbilical Cord Matrix Cells

¹ Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
² Department of Pharmacology and Toxicology, University of Kansas, Lawrence, Kansas
³ Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

^* To whom correspondence should be addressed. E-mail: xuy{at}anes.upmc.edu.

	Abstract

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 randomized into four groups: (A) sham operated, (B) 8-min CA without pretreatment, (C) 8-min CA pretreated with defined media, and (D) 8-min CA pretreated with Oct-4⁺ RUCM cells. Pretreatment was done 3 days before CA by 2.5-µl microinjection of defined media or 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 (3-4%) was found in sham group, whereas 50-68% CA1 pyramidal neurons were injured in Groups B and C. Pretreatment with Oct-4⁺ RUCM cells significantly (p<0.001) 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 non-focal 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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