Cell therapy using iPS derived cells for hearing loss against the degenerations of various cochlear cell types

• Project/Area Number: 25670721
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Otorhinolaryngology
• Research Institution: Juntendo University
• Principal Investigator: IKEDA Katsuhisa 順天堂大学, 医学部, 教授 (70159614)
• Co-Investigator(Kenkyū-buntansha): KAMIYA Kazusaku 順天堂大学, 医学部, 准教授 (10374159) ; IIZUKA Takashi 順天堂大学, 医学部, 助教 (40372932)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 聴覚障害 / 人工多能性幹細胞 / 内耳 / 有毛細胞 / ラセン神経節細胞 / 分化誘導 / 細胞治療 / 再生医療 / 遺伝性難聴 / iPS細胞 / 内耳前駆細胞 / 多能性幹細胞 / 幹細胞ホーミング / 内耳有毛細胞 / 蝸牛線維細胞

Outline of Final Research Achievements

In this study, we co-cultured iPS-derived cells with three different regions of the cochlear tissue and induced their differentiation into various types of inner cells. The number of Nanog-positive colonies with reporter GFP controlled by Nanog promotor was counted to assess the undifferentiated level of the cells. In the co-cultured cells with spiral ganglion, many cells with neurite-like protrusions were observed among the colonies. In the co-culture with the organ of Corti and spiral limbus (OC/SL), neuron-like cells were observed on the cell layer with tight junction-like adhesions. In the co-culture with the cochlear lateral wall, many cell layers with tight junction-like adhesions were observed, while undifferentiated Nanog-positive colonies were not observed. It was suggested that differentiation of iPS cells to cochlear cells was regulated depending on the part of the co-cultured organs.

Research Products

• [Journal Article] Perinatal Gjb2 gene transfer rescues hearing in a mouse model of hereditary deafness. (2015)
  • Author(s): Iizuka T, Kamiya K, Gotoh S, Sugitani Y, Suzuki M, Noda T, Minowa O, Ikeda K.
  • Journal Title: Hum Mol Genet. Volume: epub
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Assembly of the cochlear gap junction macromolecular complex requires connexin 26. (2014)
  • Author(s): Kamiya K, Yum SW, Kurebayashi N, Muraki M, Ogawa K, Karasawa K, Miwa A, Guo X, Gotoh S, Sugitani Y, Yamanaka H, Ito-Kawashima S, Iizuka T, Sakurai T, Noda T, Minowa O, Ikeda K.
  • Journal Title: J Clin Invest, Volume: 124 Issue: 4 Pages: 1598-1607
  • DOI: 10.1172/jci67621
  • Peer Reviewed / Open Access
• [Journal Article] Deficiency of Transcription Factor Brn4 Disrupts Cochlear Gap Junction Plaques in a Model of DFN3 Non-Syndromic Deafness. (2014)
  • Author(s): Kidokoro Y, Karasawa K, Minowa O, Sugitani Y., Noda T, Ikeda K, Kamiya K.
  • Journal Title: PLoS One. Volume: 9(9) Issue: 9 Pages: e108216-e108216
  • DOI: 10.1371/journal.pone.0108216
  • Peer Reviewed / Open Access
• [Journal Article] Dominant negative connexin26 mutation R75W causing severe hearing loss influences normal programmed cell death in postnatal organ of Corti (2014)
  • Author(s): Ayako Inoshita, Keiko Karasawa, Megumi Funakubo, Asuka Miwa, Katsuhisa Ikeda, Kazusaku Kamiya
  • Journal Title: BMC genetics Volume: 15(1) Issue: 1 Pages: 1-8
  • DOI: 10.1186/1471-2156-15-1
  • Peer Reviewed / Open Access
• [Journal Article] Treatment with 17-allylamino-17-demethoxygeldanamycin ameliorated symptoms of Bartter syndrome type caused by mutated Bsnd in mice. (2013)
  • Author(s): Nomura N, Kamiya K, Ikeda K, Yui N, Chiga M, Sohara E, Rai T, Sasaki S, Uchida S.
  • Journal Title: Biochem Biophys Res Commun. Volume: 441 Issue: 3 Pages: 544-49
  • DOI: 10.1016/j.bbrc.2013.10.129
  • Peer Reviewed
• [Journal Article] 遺伝性難聴への内耳細胞治療法開発 Cell therapy for hereditary hearing loss with stem cell homing factors. (2013)
  • Author(s): 神谷和作
  • Journal Title: 日本薬理学雑誌 Volume: 141(4) Pages: 191-4
  • Peer Reviewed