Tridermal tumorigenesis of induced pluripotent stem cells transplanted in ischemic brain

Hiromi Kawai, Toru Yamashita, Yasuyuki Ohta, Kentaro Deguchi, Shoko Nagotani, Xuemei Zhang, Yoshio Ikeda, Tohru Matsuura, Koji Abe

Research output: Contribution to journalArticle

150 Citations (Scopus)

Abstract

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 × 105) 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 MCAOiPS group was delayed as compared with the MCAOPBS (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.

Original languageEnglish
Pages (from-to)1487-1493
Number of pages7
JournalJournal of Cerebral Blood Flow and Metabolism
Volume30
Issue number8
DOIs
Publication statusPublished - Aug 2010

Keywords

  • cell transplantation
  • cerebral ischemia
  • induced pluripotent stem cell
  • tumorigenesis

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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