Potential treatment of cerebral global ischemia with Oct-4+ umbilical cord matrix cells.
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-microl microinjection of defined media or approximately 10(4) 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.
Jomura
Sachiko
S
Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15260, USA.
Uy
Marc
M
Mitchell
Kathy
K
Dallasen
Renee
R
Bode
Claudia J
CJ
Xu
Yan
Y
D000818:Animals; D002545:Brain Ischemia / Q000473:pathology / Q000628:therapy*; D017931:DNA Primers; D004195:Disease Models, Animal; D053595:Embryonic Stem Cells / Q000378:metabolism* / Q000637:transplantation*; D005260:Female; D005434:Flow Cytometry; D006323:Heart Arrest; D050814:Octamer Transcription Factor-3 / Q000502:physiology / Q000627:therapeutic use*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014470:Umbilical Cord
D017931:DNA Primers; D050814:Octamer Transcription Factor-3