Tridermal tumorigenesis of induced pluripotent stem cells transplanted in ischemic brain.
Stroke is a major neurologic disorder. Induced pluripotent stem (iPS) cells can be produced from basically any part of patients, with high reproduction ability and pluripotency to differentiate into various types of cells, suggesting that iPS cells can provide a hopeful therapy for cell transplantation. However, transplantation of iPS cells into ischemic brain has not been reported. In this study, we showed that the iPS cells fate in a mouse model of transient middle cerebral artery occlusion (MCAO). Undifferentiated iPS cells (5 x 10(5)) were transplanted into ipsilateral striatum and cortex at 24 h after 30 mins of transient MCAO. Behavioral and histologic analyses were performed at 28 day after the cell transplantation. To our surprise, the transplanted iPS cells expanded and formed much larger tumors in mice postischemic brain than in sham-operated brain. The clinical recovery of the MCAO+iPS group was delayed as compared with the MCAO+PBS (phosphate-buffered saline) group. iPS cells formed tridermal teratoma, but could supply a great number of Dcx-positive neuroblasts and a few mature neurons in the ischemic lesion. iPS cells have a promising potential to provide neural cells after ischemic brain injury, if tumorigenesis is properly controlled.
Kawai
Hiromi
H
Department of Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Yamashita
Toru
T
Ohta
Yasuyuki
Y
Deguchi
Kentaro
K
Nagotani
Shoko
S
Zhang
Xuemei
X
Ikeda
Yoshio
Y
Matsuura
Tohru
T
Abe
Koji
K
D000818:Animals; D001921:Brain / Q000166:cytology / Q000473:pathology* / Q000601:surgery; D002545:Brain Ischemia / Q000473:pathology / Q000601:surgery / Q000628:therapy; D002470:Cell Survival; D000089662:Doublecortin Protein; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000473:pathology / Q000637:transplantation*; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology / Q000601:surgery* / Q000628:therapy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity; D009385:Neoplastic Processes; D055495:Neurogenesis