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Open Access Fates of Murine Pluripotent Stem Cell-Derived Neural Progenitors Following Transplantation Into Mouse Cochleae

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Abstract:

This study evaluated the tumorigenesis risk of induced pluripotent stem (iPS) cells after transplantation into the cochlea. One mouse embryonic stem (ES) cell line and three mouse iPS cell lines, one derived from adult mouse tail-tip fibroblasts (TTFs) and two from mouse embryonic fibroblasts (MEFs), were neurally induced by stromal cell-inducing activity. Before transplantation, the efficiency of neural induction and the proportion of residual undifferentiated cells were evaluated using immunocytochemistry, and no significant differences were observed in the ratios of colonies expressing βIII tubulin, nestin, or octamer (Oct)3/4. Four weeks after transplantation into the cochleae of neonatal mice, the number of surviving transplants of TTF-derived iPS cells generated by retroviral infection was significantly higher than those of MEF-derived iPS cells generated by plasmid transfection. Teratoma formation was identified in one of five cochleae transplanted with TTF-derived iPS cells. However, no significant differences were found in the cell proliferation activity or the extent of differentiation into mature neurons among the cell lines. These findings emphasize the necessity of selecting appropriate iPS cell lines and developing methods to eliminate undifferentiated cells after neural induction, in order to establish safe iPS cell-based therapy for the inner ear.

Keywords: Cell therapy; Hearing loss; Inner ear; Pluripotent stem cell; Teratoma

Document Type: Research Article

DOI: http://dx.doi.org/10.3727/096368911X623907

Affiliations: Department of Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan

Publication date: April 1, 2012

More about this publication?
  • Cell Transplantation publishes original, peer-reviewed research and review articles on the subject of cell transplantation and its application to human diseases. To ensure high-quality contributions from all areas of transplantation, separate section editors and editorial boards have been established. Articles deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, among others. Basic clinical studies and immunological research papers are also featured. To provide complete coverage of this revolutionary field, Cell Transplantation will report on relevant technological advances, and ethical and regulatory considerations of cell transplants. Cell Transplantation is now an Open Access journal starting with volume 18 in 2009, and therefore there will be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow work to be disseminated to a wider audience and also entitle the corresponding author to a free PDF, as well as prepublication of an unedited version of the manuscript.
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