Treatment of hypoxic–ischemic encephalopathy in mouse by transplantation of embryonic stem cell-derived cells

• Published in: Neurochemistry international 2007-07, Vol.51 (1), p.57-65
• Main Authors: Ma, Jie, Wang, Yu, Yang, Jianhua, Yang, Min, Chang, Keun-A, Zhang, Linhua, Jiang, Feng, Li, Yi, Zhang, Zhonggong, Heo, Chaejeong, Suh, Yoo-Hun
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Biological and medical sciences; Biomarkers - analysis; Biomarkers - metabolism; Brain Infarction - metabolism; Brain Infarction - physiopathology; Brain Infarction - therapy; Cell Differentiation - physiology; Cell Line; Cells transplantation; Cerebral Cortex - metabolism; Cerebral Cortex - pathology; Cerebral Cortex - physiopathology; Embryonic neural stem cell; Embryonic Stem Cells - metabolism; Embryonic Stem Cells - transplantation; Fundamental and applied biological sciences. Psychology; Graft Survival - physiology; Hippocampus - metabolism; Hippocampus - pathology; Hippocampus - physiopathology; Hypoxia-Ischemia, Brain - metabolism; Hypoxia-Ischemia, Brain - physiopathology; Hypoxia-Ischemia, Brain - therapy; Hypoxic–ischemic encephalopathy; Intermediate Filament Proteins - genetics; Memory Disorders - metabolism; Memory Disorders - physiopathology; Memory Disorders - therapy; Mice; Mice, Inbred C57BL; Microtubule-Associated Proteins - genetics; Neonatal mouse; Nerve Degeneration - metabolism; Nerve Degeneration - physiopathology; Nerve Degeneration - therapy; Nerve Tissue Proteins - genetics; Nestin; Neurons - metabolism; RNA, Messenger - metabolism; Stem Cell Transplantation - methods; Treatment Outcome; Vertebrates: nervous system and sense organs
• ISSN: 0197-0186; 1872-9754
• DOI: 10.1016/j.neuint.2007.04.012

A 7-day-old hypoxic–ischemic encephalopathy (HIE) mouse model was used to study the effect of transplantation of embryonic stem (ES) cell-derived cells on the HIE. After the inducement in vitro, the ES cell-derived cells expressed Nestin and MAP-2, rather than GFAP mRNA. After transplantation, ES cell-derived cells can survive, migrate into the injury site, and specifically differentiate into neurons, showing improvement of the learning ability and memory of the HIE mouse at 8 months post-transplantation. The non-grafted HIE mouse brain showed typical pathological changes in the hippocampus and cerebral cortex, where the number of neurons was reduced, while in the cell graft group, number of the neurons increased in the same regions. Although further study is necessary to elucidate the precise mechanisms responsible for this functional recovery, we believe that ES cells have advantages for use as a donor source in HIE.