Transplantation of neural cells derived from retinoic acid-treated cynomolgus monkey embryonic stem cells successfully improved motor function of hemiplegic mice with experimental brain injury.
We induced neural cells by treating cynomolgus monkey embryonic stem (ES) cells with retinoic acid. The treated cells mainly expressed betaIIItubulin. They further differentiated into neurons expressing neurofilament middle chain (NFM) in elongated axons. Half of the cells differentiated into Islet1+ motoneurons in vitro. The monkey ES-derived neural cells were transplanted to hemiplegic mice with experimental brain injury mimicking stroke. The neural cells that had grafted into periventricular area of the mice distributed extensively over the injured cortex. Some of the transplanted cells expressed the neural stem/progenitor marker nestin 2 days after transplantation. The cells expressed markers characteristic of mature motoneurons 28 days after transplantation. Mice with the neural cell graft gradually recovered motor function, whereas control animals remained hemiplegic. This is the first demonstration that neural cells derived from nonhuman primate ES cells have the ability to restore motor function in an animal model of brain injury.
Ikeda
Ritsuko
R
Department of Immunology, St. Marianna University School of Medicine, 2-16-1, Sugao, Kawasaki, Kanagawa 216-8511, Japan.
Kurokawa
Manae S
MS
Chiba
Shunmei
S
Yoshikawa
Hideshi
H
Ide
Michiko
M
Tadokoro
Mamoru
M
Nito
Shinji
S
Nakatsuji
Norio
N
Kondoh
Yasushi
Y
Nagata
Ken
K
Hashimoto
Takuo
T
Suzuki
Noboru
N
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001925:Brain Damage, Chronic / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D002544:Cerebral Infarction / Q000150:complications / Q000503:physiopathology / Q000628:therapy; D004195:Disease Models, Animal; D005260:Female; D006085:Graft Survival / Q000502:physiology; D006429:Hemiplegia / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008252:Macaca fascicularis; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D064231:Nestin; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology / Q000637:transplantation*; D020127:Recovery of Function / Q000502:physiology*; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology; D020521:Stroke / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D016896:Treatment Outcome; D014212:Tretinoin / Q000494:pharmacology
D015415:Biomarkers; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D016900:Neurofilament Proteins; C061195:neurofilament protein M; D014212:Tretinoin