CD133+ cells from human umbilical cord blood reduce cortical damage and promote axonal growth in neonatal rat organ co-cultures exposed to hypoxia.
To evaluate the effect of CD133(+) cells (endothelial progenitor cells) on the hypoxia-induced suppression of axonal growth of cortical neurons and the destruction of blood vessels (endothelial cells), we used anterograde axonal tracing and immunofluorescence in organ co-cultures of the cortex and the spinal cord from 3-day-old neonatal rats. CD133(+) cells prepared from human umbilical cord blood were added to the organ co-cultures after hypoxic insult, and axonal growth, vascular damage and apoptosis were evaluated. Anterograde axonal tracing with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate was used to analyze axonal projections from the cortex to the spinal cord. Immunolabeling co-cultured tissues of the cortex and the spinal cord were used to investigate the effect of CD133(+) cells on the survival of blood vessels and apoptosis in the brain cortex. Hypoxia remarkably suppressed axonal growth in organ co-cultures of the cortex and the spinal cord, and this suppression was significantly restored by the addition of CD133(+) cells. CD133(+) cells also reduced the hypoxia-induced destruction of the cortical blood vessels and apoptosis. CD133(+) cells had protective effects on hypoxia-induced injury of neurons and blood vessels of the brain cortex in vitro. These results suggest that CD133(+) cell transplantation may be a possible therapeutic intervention for perinatal hypoxia-induced brain injury.
Tanaka
Norifumi
N
Department of Obstetrics and Gynecology, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima, 734-8551, Japan.
Kamei
Naosuke
N
Nakamae
Toshio
T
Yamamoto
Risako
R
Ishikawa
Masakazu
M
Fujiwara
Hisaya
H
Miyoshi
Hiroshi
H
Asahara
Takayuki
T
Ochi
Mitsuo
M
Kudo
Yoshiki
Y
D000071916:AC133 Antigen; D000818:Animals; D000831:Animals, Newborn; D015703:Antigens, CD / Q000276:immunology*; D017209:Apoptosis; D001369:Axons / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000033:anatomy & histology / Q000196:embryology / Q000378:metabolism / Q000473:pathology*; D002560:Cerebrovascular Circulation; D018920:Coculture Techniques; D005312:Fetal Blood / Q000166:cytology*; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D000860:Hypoxia; D010455:Peptides / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D046509:Tissue Culture Techniques
D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606025:Prom1 protein, rat