Transplantation of mouse induced pluripotent stem cells into the cochlea

This study examined the potential of induced pluripotent stem (iPS) cells for use as a source of transplants for the restoration of auditory spiral ganglion neurons. We monitored neurite outgrowth from iPS cell-derived neural progenitors toward cochlear hair cells ex vivo, and followed their survival and fates after transplantation into mouse cochleae in vivo. Neurons derived from iPS cells projected neurites toward cochlear hair cells. The settlement of iPS cell-derived neurons was observed 1 week after transplantation into the cochlea. Some transplants expressed vesicular glutamate transporter 1, which is a marker for glutamatergic neurons. These findings indicate that iPS cells can be used as a source of transplants for the regeneration of spiral ganglion neurons.

[1]  Huawei Li,et al.  Stem cells as therapy for hearing loss. , 2004, Trends in molecular medicine.

[2]  R. Altschuler,et al.  Glutamatergic Neuronal Differentiation of Mouse Embryonic Stem Cells after Transient Expression of Neurogenin 1 and Treatment with BDNF and GDNF: In Vitro and In Vivo Studies , 2008, The Journal of Neuroscience.

[3]  J. Frisén,et al.  Survival and neural differentiation of adult neural stem cells transplanted into the mature inner ear. , 2005, Experimental cell research.

[4]  E. Rubel,et al.  Cell division in the gerbil cochlea after acoustic trauma. , 1994, The American journal of otology.

[5]  J. Ito,et al.  A Novel Model for Rapid Induction of Apoptosis in Spiral Ganglions of Mice , 2003, The Laryngoscope.

[6]  J. Ito,et al.  Engraftment of embryonic stem cell-derived neurons into the cochlear modiolus , 2005, Neuroreport.

[7]  R. Shepherd,et al.  Concise Review: The Potential of Stem Cells for Auditory Neuron Generation and Replacement , 2007, Stem cells.

[8]  T. Nakagawa,et al.  Cell therapy for inner ear diseases. , 2005, Current pharmaceutical design.

[9]  T. Nikolopoulos,et al.  Sensory Cell Regeneration and Stem Cells: What We Have Already Achieved in the Management of Deafness , 2008, Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology.

[10]  K. Omori,et al.  Transplantation of neural stem cells into the modiolus of mouse cochleae injured by cisplatin. , 2004, Acta oto-laryngologica. Supplementum.

[11]  K. Mizuseki,et al.  Induction of Midbrain Dopaminergic Neurons from ES Cells by Stromal Cell–Derived Inducing Activity , 2000, Neuron.

[12]  E. Keithley,et al.  Spiral ganglion cell density in young and old gerbils , 1989, Hearing Research.

[13]  Huawei Li,et al.  Engraftment and differentiation of embryonic stem cell-derived neural progenitor cells in the cochlear nerve trunk: growth of processes into the organ of Corti. , 2006, Journal of neurobiology.

[14]  松本 昌宏 Innervation of stem cell-derived neurons into auditory epithelia of mice , 2008 .

[15]  Takashi Aoi,et al.  Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts , 2008, Nature Biotechnology.

[16]  M. Monk,et al.  HPRT-deficient (Lesch–Nyhan) mouse embryos derived from germline colonization by cultured cells , 1987, Nature.

[17]  S. Yamanaka,et al.  Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors , 2006, Cell.

[18]  T. Ichisaka,et al.  Generation of germline-competent induced pluripotent stem cells , 2007, Nature.

[19]  F. Fujiyama,et al.  Potential of embryonic stem cell‐derived neurons for synapse formation with auditory hair cells , 2008, Journal of neuroscience research.