Differentiation to the functional retina cell using tissue stem/progenitor cell and iPS cell derived from human iris tissue.

• Project/Area Number: 17K11495
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Fujita Health University
• Principal Investigator: Yamamoto Naoki 藤田医科大学, 共同利用研究設備サポートセンター, 准教授 (00267957)
• Co-Investigator(Kenkyū-buntansha): 谷川 篤宏 藤田医科大学, 医学部, 准教授 (40324412) ; 大熊 真人 藤田医科大学, 医学部, 講師 (50329710) ; 堀口 正之 藤田医科大学, 医学部, 教授 (70209295) ; 宮地 栄一 藤田医科大学, 医学部, 教授 (90129685)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: iPS細胞 / 網膜再生 / 再生医療 / 虹彩細胞 / 網膜神経細胞 / 電気生理 / 組織幹細胞 / 不死化細胞 / 組織幹／前駆細胞 / 創薬研究

Outline of Final Research Achievements

We investigated inhibitors and coating agents, and established a culture method that can maintain the status of tissue stem cells relatively well. This culture method is a preliminarily designed to maintain the status of tissue stem cells and cancer stem cells.
Human iris-derived iPS cells were able to differentiate into retinal ganglion cells and retinal neurons with electrophysiological functions. Iris-derived iPS cells were more likely to differentiate into ectodermal cells in gene panel tests than iPS cells derived from other tissues. Iris-derived iPS cells were subjected to non-adherent (floating) and rotational floating culture method, and two types of cell aggregates were formed: one of cell mass with vacuous interior and another of cell aggregate exhibiting a substantial neural retina cell layer structure.

Academic Significance and Societal Importance of the Research Achievements

眼球の網膜は，視細胞をはじめとする神経細胞の集まりです。眼の視力を再生させるためには、この網膜神経細胞の遺伝子やタンパク質を発現する細胞をiPS細胞から再生させるだけでは意味がなく、神経細胞としての機能を有する細胞でなければなりません。
私たちの研究では、iPS細胞から神経細胞としての機能を有する細胞に成長させる研究を行っています。将来的には、自身の眼球から安全に採取する術式が確立されている虹彩細胞を用いて、iPS細胞を作製するオーダーメード再生医療や網膜神経の再生・回復を補助する創薬開発の評価で使用できる細胞を作出し、網膜疾患の患者さんに貢献できる研究を行っていきます。

Research Products

• [Journal Article] Mechanism of atopic cataract caused by eosinophil granule major basic protein. (2019)
  • Author(s): Yamamoto N., Hiramatsu N., Isogai S., Kondo M., Imaizumi K., Horiguchi M.
  • Journal Title: Med Mol Morphol. Volume: Online ahead of print Issue: 2 Pages: 94-103
  • DOI: 10.1007/s00795-019-00234-5
  • Peer Reviewed
• [Journal Article] An Analysis of Monocytes and Dendritic Cells Differentiated From Human Peripheral Blood Monocyte-Derived Induced Pluripotent Stem Cells (2019)
  • Author(s): Hiramatsu N, Yamamoto N, Isogai S, Onouchi T, Hirayama M, Maeda S, Ina T, Kondo M, Imaizumi K.
  • Journal Title: Med Mol Morphol. Volume: - Issue: 2 Pages: 63-72
  • DOI: 10.1007/s00795-019-00231-8
  • Peer Reviewed
• [Journal Article] The Correlation of Fluorescence of Protoporphyrinogen IX and Status of Isocitrate Dehydrogenase in Gliomas (2019)
  • Author(s): Ohba Shigeo、Murayama Kazuhiro、Kuwahara Kiyonori、Pareira Eriel Sandika、Nakae Shunsuke、Nishiyama Yuya、Adachi Kazuhide、Yamada Seiji、Sasaki Hikaru、Yamamoto Naoki、Abe Masato、Mukherjee Joydeep、Hasegawa Mitsuhiro、Pieper Russell O、Hirose Yuichi
  • Journal Title: Neurosurgery Volume: - Issue: 2 Pages: 408-417
  • DOI: 10.1093/neuros/nyz524
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Cytokine expression profiles in cervical mucus from patients with cervical cancer and its precursor lesions (2019)
  • Author(s): Otani S, Fujii T, Kukimoto I, Yamamoto N, Tsukamoto T, Ichikawa R, Nishio E, Iwata A.
  • Journal Title: Cytokine Volume: 120 Pages: 210-219
  • DOI: 10.1016/j.cyto.2019.05.011
  • Peer Reviewed / Open Access
• [Journal Article] CXCL12 regulates differentiation of human immature melanocyte precursors as well as their migration. (2019)
  • Author(s): Yamada T, Hasegawa S, Hasebe Y, Kawagishi-Hotta M, Arima M, Iwata Y, Kobayashi T, Numata S, Yamamoto N, Nakata S, Sugiura K, Akamatsu H.
  • Journal Title: Arch Dermatol Res Volume: 311 Issue: 1 Pages: 55-62
  • DOI: 10.1007/s00403-018-1880-2
  • Peer Reviewed
• [Journal Article] Laminin-332 regulates differentiation of human interfollicular epidermal stem cells. (2018)
  • Author(s): Yamada T., Hasegawa S., Miyachi K., Date Y., Inoue Y., Yagami A., Arima M., Iwata Y., Yamamoto N., Nakata S., Matsunaga K., Sugiura K., Akamatsu H.
  • Journal Title: Mech Ageing Dev. Volume: 171 Pages: 37-46
  • DOI: 10.1016/j.mad.2018.03.007
  • Peer Reviewed
• [Journal Article] Preparation of induced pluripotent stem cells using human peripheral blood monocytes. (2018)
  • Author(s): Isogai S., Yamamoto N., Hiramatsu N., Goto Y., Hayashi M., Kondo M., Imaizumi K.
  • Journal Title: Cell Reprogram. Volume: 20 Issue: 6 Pages: 347-355
  • DOI: 10.1089/cell.2018.0024
  • Peer Reviewed / Open Access
• [Journal Article] Extracellular proteoglycan decorin maintains human hair follicle stem cells. (2018)
  • Author(s): Miyachi K., Yamada T., Kawagishi-Hotta M., Hasebe Y., Date Y., Hasegawa S., Arima M., Iwata Y., Kobayashi T., Numata S., Yamamoto N., Nakata S., Sugiura K, Akamatsu H.
  • Journal Title: J Dermatol. Volume: 45 Issue: 12 Pages: 1403-1410
  • DOI: 10.1111/1346-8138.14678
  • Peer Reviewed
• [Journal Article] A proteomic approach for understanding the mechanisms of delayed corneal wound healing in diabetic keratopathy using diabetic model rat. (2018)
  • Author(s): Ymamoto T., Otake H., Hiramatsu N., Yamamoto N., Taga A., Nagai N.
  • Journal Title: Int J Mol Sci Volume: 19 Issue: 11 Pages: 3635-3635
  • DOI: 10.3390/ijms19113635
  • Peer Reviewed
• [Journal Article] Vasopressin-secreting neurons derived from human embryonic stem cells through specific induction of dorsal hypothalamic progenitors (2018)
  • Author(s): Koichiro Ogawa, Hidetaka Suga, Chikafumi Ozone, Mayuko Kano, Kazuki Mitsumoto, Takatoshi Kasai, Yu Kodani, Hiroshi Nagasaki, Naoki Yamamoto, Daisuke Hagiwara, Motomitsu Goto, Ryoichi Banno, Yoshihisa Sugimura, and Hiroshi Arima
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 3615-3615
  • DOI: 10.1038/s41598-018-22053-x
  • Peer Reviewed / Open Access
• [Journal Article] Ophthalmic formulation containing nilvadipine nanoparticles prevents retinal dysfunction in rats Injected with streptozotocin. (2017)
  • Author(s): Deguchi S., Otake H., Nakazawa Y., Hiramatsu N., Yamamoto N., Nagai N.
  • Journal Title: Int J Mol Sci Volume: 18 Issue: 12 Pages: 2720-2720
  • DOI: 10.3390/ijms18122720
  • Peer Reviewed / Open Access
• [Journal Article] Therapeutic Effect of Cilostazol Ophthalmic Nanodispersions on Retinal Dysfunction in Streptozotocin-Induced Diabetic Rats. (2017)
  • Author(s): Nagai N., Deguchi S., Otake H., Hiramatsu N., Yamamoto N.
  • Journal Title: Int J Mol Sci Volume: 18 Issue: 9 Pages: 1971-1971
  • DOI: 10.3390/ijms18091971
  • Peer Reviewed / Open Access
• [Journal Article] TALEN-mediated shift of mitochondrial DNA heteroplasmy in MELAS-iPSCs with m.13513G>A mutation. (2017)
  • Author(s): Yahata N., Matsumoto Y., Omi M., Yamamoto N., Hata R.
  • Journal Title: Sci Rep. Volume: 7 Issue: 1 Pages: 15557-15557
  • DOI: 10.1038/s41598-017-15871-y
  • Peer Reviewed / Open Access
• [Journal Article] Enhancement of individual differences in proliferation and differentiation potentials of aged human adipose-derived stem cells. (2017)
  • Author(s): Kawagishi-Hotta M., Hasegawa S., Igarashi T., Yamada T., Takahashi M, Numata S., Kobayashi T., Iwata Y., Arima M., Yamamoto N., Yagami A., Nakata S., Uzawa T, Matsunaga K, Sugiura K., Akamatsu H.
  • Journal Title: Regenerative Therapy Volume: 6 Pages: 29-40
  • DOI: 10.1016/j.reth.2016.12.004
  • Peer Reviewed / Open Access
• [Journal Article] Promethazine hydrochloride inhibits ectopic fat cell formation in skeletal musce. (2017)
  • Author(s): Kasai T, Tsuchida, K. et al.,
  • Journal Title: Am. J. Pathol. Volume: 187 Issue: 12 Pages: 2627-2634
  • DOI: 10.1016/j.ajpath.2017.08.008
  • Peer Reviewed / Open Access
• [Journal Article] Identification of novel splicing variants of protein tyrosine phosphatase receptor type Z (2017)
  • Author(s): Fujikawa Akihiro、Chow Jeremy Pak Hong、Matsumoto Masahito、Suzuki Ryoko、Kuboyama Kazuya、Yamamoto Naoki、Noda Masaharu
  • Journal Title: The Journal of Biochemistry Volume: 162 Issue: 5 Pages: 381-390
  • DOI: 10.1093/jb/mvx042
  • NAID: 40021394892
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] SEAM法を応用した虹彩由来iPS細胞の網膜神経節細胞への分化誘導． (2019)
  • Author(s): 山本直樹、平松範子、大熊真人、磯谷澄都、谷川篤宏、今泉和良、宮地栄一、堀口正之．
  • Organizer: 第51回日本臨床分子形態学会総会・学術集会
• [Presentation] 混濁水晶体や眼内レンズと創傷治癒－透明水晶体の再生に向けて－ (2019)
  • Author(s): 山本直樹
  • Organizer: 第23回眼創傷治癒研究会
  • Invited
• [Presentation] 基礎研究から拓かれる応用研究・開発研究 水晶体・白内障研究の魅力． (2019)
  • Author(s): 山本直樹
  • Organizer: 第58回日本白内障学会総会・第45回水晶体研究会合同学会
• [Presentation] Evaluation of corneal damage recovery using 3-dimensional model. (2019)
  • Author(s): Kojima H., Kato Y., Sato A., Yamamoto N.
  • Organizer: 58th annual meeting & ToxExpo, Society of Toxicology.
  • Int'l Joint Research
• [Presentation] アレルギー疾患に合併する白内障の発症メカニズム． (2019)
  • Author(s): 山本直樹、平松範子、磯谷澄都、堀口正之、平野耕治、近藤征史、今泉和良．
  • Organizer: 第28回国際喘息学会日本・北アジア部会
  • Int'l Joint Research
• [Presentation] 今話題の白内障研究・治療を検証する 水晶体再生治療はできるのか？ (2018)
  • Author(s): 山本直樹
  • Organizer: 第57回日本白内障学会総会・第43回水晶体研究会合同学会
  • Invited
• [Presentation] 組織学の解析入門と組織標本からの研究展開 －透明水晶体と後発白内障の組織学的解析を中心に－． (2018)
  • Author(s): 山本直樹
  • Organizer: 第33回JSCRS学術総会
  • Invited
• [Presentation] Development of the in vitro assay for evaluating reversible eye irritation. (2018)
  • Author(s): Yamamoto N., Hiramatsu N., Kato Y., Kojima H.
  • Organizer: 10th World Congress on Alternatives & Animal Use in the Life Sciences.
  • Int'l Joint Research
• [Presentation] Development of the in vitro assay for evaluating weak eye irritation. (2018)
  • Author(s): Yamamoto N., Hiramatsu N., Kato Y., Kojima H.
  • Organizer: 10th World Congress on Alternatives & Animal Use in the Life Sciences.
  • Int'l Joint Research
• [Presentation] 虹彩由来iPS細胞を用いた水晶体上皮細胞への分化誘導． (2018)
  • Author(s): 山本 直樹, 平松 範子, 大熊 真人, 磯谷 澄都, 谷川 篤宏, 今泉 和良, 宮地 栄一, 堀口 正之
  • Organizer: 第50回日本臨床分子形態学会総会・学術集会
• [Presentation] Development of the in vitro assay for evaluating weak eye irritation. (2017)
  • Author(s): Naoki Yamamoto, Noriko Hiramatsu, Yoshinao Kato, Hajime Kojima
  • Organizer: WC10 Seattle ALTEX
  • Int'l Joint Research
• [Presentation] 虹彩由来細胞を用いたiPS細胞作出と生理的機能を有する神経細胞への分化誘導 (2017)
  • Author(s): 山本 直樹, 大熊 真人, 平松 範子, 磯谷 澄都, 今泉 和良, 谷川 篤宏, 宮地 栄一, 堀口 正之
  • Organizer: 日本組織培養学会第90回大会
• [Presentation] 【学会奨励賞受賞記念講演】組織幹/前駆細胞・不死化細胞・iPS細胞を用いた 網膜再生研究 (2017)
  • Author(s): 山本直樹
  • Organizer: 第49回日本臨床分子形態学会総会・学術集会
  • Invited
• [Presentation] 三次元角膜再構築モデルを用いて 回復性は評価できるか？ (2017)
  • Author(s): 山本直樹
  • Organizer: 日本動物実験代替法学会 第30回大会
  • Invited
• [Book] 皮膚の安全性・有用性評価法 (2018)
  • Author(s): 山本直樹（分担著者）
  • Total Pages: 332
  • Publisher: 技術情報協会
  • ISBN: 4861047129
• [Remarks] 藤田医科大学 研究成果検索ページ
  • URL: https://pure.fujita-hu.ac.jp/ja/publications/
• [Remarks]
  • URL: https://www.fujita-hu.ac.jp/achievements/
• [Remarks]
  • URL: https://researchmap.jp/read0136071
• [Remarks]
  • URL: https://www.scopus.com/authid/detail.uri?authorId=55599876800