Fundamental medical research of the retinal regeneration using tissue stem / progenitor cells, immortalized cells, induced pluripotent stem cells derived from iris tissue.

• Project/Area Number: 26462701
• 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: Naoki Yamamoto 藤田保健衛生大学, 共同利用研究推進施設, 准教授 (00267957)
• Co-Investigator(Kenkyū-buntansha): 谷川 篤宏 藤田保健衛生大学, 医学部, 准教授 (40324412) ; 大熊 真人 藤田保健衛生大学, 医学部, 講師 (50329710) ; 堀口 正之 藤田保健衛生大学, 医学部, 教授 (70209295) ; 宮地 栄一 藤田保健衛生大学, 医学部, 教授 (90129685)
• Research Collaborator: IMAIZUMI Kazuyosi ; ISOGAI Sumito ; HIRAMATSU Noriko ; YAMASHITA Hiromi ; YAMADA Harumoto ; TAJIMA Kaori
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: iPS細胞 / 網膜再生 / 不死化細胞 / 組織幹／前駆細胞 / 再生医療 / 電気生理 / 虹彩 / 虹彩由来iPS細胞 / 網膜幹／前駆細胞 / 組織幹細胞 / 網膜幹/前駆細胞

Outline of Final Research Achievements

We discovered that the iris tissue stem / progenitor cells could culture for a long term by the coating agent and the repressor using culture methods of the induced pluripotent stem (iPS) cells.
The immortalization cells and the iPS cells derived from iris were able to differentiate for the expression of specific for nerve and retina cell marker by using the two phases-style new differentiation method. These differentiated cells had the physiologic neurotransmission nerve cell function. In addition, after comparing the iPS cells of the different origin cell, iPS cells derived from iris had better the cell shape and maintenance culture as nerve cells.

Research Products

• [Journal Article] 新たな手法で作出した不死化細胞による医薬品・医薬部外品の評価． (2017)
  • Author(s): 山本直樹
  • Journal Title: 眼薬理 Volume: 31
  • Peer Reviewed
• [Journal Article] Establishment of a new immortalized human corneal epithelial cell line (iHCE-NY1) for use in evaluating eye irritancy by in vitro test methods. (2016)
  • Author(s): Yamamoto N, Kato Y, Sato A, Hiramatsu N, Yamashita H, Ohkuma M, Miyachi E, Horiguchi M, Hirano K, Kojima H.
  • Journal Title: In Vitro Cell Dev Biol Anim. Volume: 52 Issue: 7 Pages: 742-748
  • DOI: 10.1007/s11626-016-0038-9
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Cell-surface protein profiling identifies distinctive markers of progenitor cells in human skeletal muscle. (2016)
  • Author(s): Uezumi A, Nakatani M, Ikemoto-Uezumi M, Yamamoto N, Morita M, Yamaguchi A, Yamada H, Kasai T, Masuda S, Narita A, Miyagoe-Suzuki Y, Takeda S, Fukada S, Nishino I, Tsuchida K.
  • Journal Title: Stem Cell Reports. Volume: 7 Issue: 2 Pages: 263-278
  • DOI: 10.1016/j.stemcr.2016.07.004
  • Peer Reviewed / Open Access
• [Journal Article] A lower volume culture method for obtaining a larger yield of neuron-like cells from mesenchymal stem cells. (2016)
  • Author(s): Shimomura A, Iizuka-Kogo A, Yamamoto N, Nomura R.
  • Journal Title: Med Mol Morphol. Volume: 49 Issue: 2 Pages: 119-126
  • DOI: 10.1007/s00795-015-0131-2
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 【総説】 虹彩由来細胞を用いた網膜再生．－組織幹/前駆細胞・不死化細胞・iPS細胞を用いて－． (2016)
  • Author(s): 山本直樹
  • Journal Title: BIO Clinica Volume: 31 Pages: 1166-1168
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Establishment of a new immortalized human corneal epithelial cell line (iHCE-NY1) for use in evaluating eye irritancy by in vitro test methods (2016)
  • Author(s): Yamamoto N., Kato Y., Sato A., Hiramatsu N., Yamashita H., Ohkuma M., Miyachi E., Horiguchi M., Hirano K., Kajima H.
  • Journal Title: In Vitro Cellular & Developmental Biology - Animal Volume: Epub ahead of print
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] In vitro antiproliferative activity of 2,3-dihydroxy-9,10-anthraquinone induced apoptosis against COLO320 cells through cytochrome c release caspase mediated pathway with PI3K/AKT and COX-2 inhibition. (2016)
  • Author(s): Balachandran C, Emi N, Arun Y, Yamamoto N, Duraipandiyan V, Inaguma Y, Okamoto A, Ignacimuthu S, Al-Dhabi NA, Perumal PT.
  • Journal Title: Chem Biol Interact Volume: 249 Pages: 23-35
  • DOI: 10.1016/j.cbi.2016.02.016
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Pro-IGF-II ameliorates age-related inefficient regenerative response by orchestrating self-reinforcement mechanism of muscle regeneration. (2015)
  • Author(s): Ikemoto-Uezumi M, Uezumi A, Tsuchida K, Fukada S, Yamamoto H, Yamamoto N, Shiomi K, Hashimoto N.
  • Journal Title: Stem Cells Volume: in press Issue: 8 Pages: 2456-2468
  • DOI: 10.1002/stem.2045
  • Peer Reviewed
• [Journal Article] Induction of HLA-B*40:02-restricted T cells possessing cytotoxic and suppressive functions against haematopoietic progenitor cells from a patient with severe aplastic anaemia. (2015)
  • Author(s): Inaguma Y, Akatsuka Y, Hosokawa K, Maruyama H, Okamoto A, Katagiri T, Shiraishi K, Murayama Y, Tsuzuki-Iba S, Mizutani Y, Nishii C, Yamamoto N, Demachi-Okamura A, Kuzushima K, Ogawa S, Emi N, Nakao S.
  • Journal Title: Br J Haematol. Volume: in press Issue: 1 Pages: 131-134
  • DOI: 10.1111/bjh.13464
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Effects of aloe-emodin and emodin on proliferation of the MKN45 human gastric cancer cell line. (2015)
  • Author(s): Chihara T, Shimpo K, Beppu H, Yamamoto N, Kaneko T, Wakamatsu K, Sonoda S.
  • Journal Title: Asian Pac J Cancer Prev. Volume: 16 Pages: 3887-3891
  • Peer Reviewed
• [Journal Article] A lower volume culture method for obtaining a larger yield of neuron-like cells from mesenchymal stem cells. (2015)
  • Author(s): Shimomura A, Iizuka-Kogo A, Yamamoto N, Nomura R.
  • Journal Title: Med Mol Morphol. Volume: Epub ahead of print
  • Peer Reviewed
• [Journal Article] Identification and characterization of PDGFRα mesenchymal progenitors in human skeletal muscle. (2014)
  • Author(s): Uezumi A, Fukada S, Yamamoto N, Ikemoto-Uezumi M, Yamada H, Nishino I, Hamada Y, Tsuchida K.
  • Journal Title: Cell Death Disease Volume: 5 Issue: 4 Pages: 1186-1186
  • DOI: 10.1038/cddis.2014.161
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Accelerated differentiation of melanocyte stem cells contributes to the formation of hyperpigmented maculae. (2014)
  • Author(s): Yamada T, Hasegawa S, Inoue Y, Date Y, Arima M, Yagami A, Iwata Y, Takahashi M, Yamamoto N, Mizutani H, Nakata S, Matsunaga K, Akamatsu H.
  • Journal Title: Exp Dermatol. Volume: 23 Issue: 9 Pages: 652-658
  • DOI: 10.1111/exd.12496
  • Peer Reviewed
• [Journal Article] Comprehensive analysis of melanogenesis and proliferation potential of melanocyte lineage in solar lentigines. (2014)
  • Author(s): Yamada T., Hasegawa S., Inoue Y., Date Y., Arima M., Yagami A., Iwata Y., Abe M., Takahashi M., Yamamoto N., Mizutani H., Nakata S., Matsunaga K., Akamatsu H.
  • Journal Title: J Dermatol Sci. Volume: 73 Issue: 3 Pages: 251-257
  • DOI: 10.1016/j.jdermsci.2013.11.005
  • Peer Reviewed
• [Presentation] iPS細胞の培養で必要なフィーダー細胞の検討． (2016)
  • Author(s): 山本直樹、平松範子、山下宏美、大熊真人、宮地栄一、磯谷澄都、今泉和良、谷川篤宏、堀口正之、谷口孝喜
  • Organizer: 第48回藤田学園医学会
  • Place of Presentation: 愛知県豊明市、フジタホール500
  • Year and Date: 2016-10-06
• [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． (2016)
  • 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: 第48回日本分子形態学会総会・学術集会
  • Place of Presentation: 熊本県熊本市、くまもと県民交流館パレア
  • Year and Date: 2016-09-23
• [Presentation] 新たな手法で作出した不死化細胞による医薬品・医薬部外品の評価． (2016)
  • Author(s): 山本直樹
  • Organizer: 第36回日本眼薬理学会
  • Place of Presentation: 東京都板橋区、帝京大学板橋キャンパス
  • Year and Date: 2016-09-10
  • Invited
• [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． (2016)
  • Author(s): 山本直樹、平松範子
  • Organizer: 第55回日本白内障学会総会・第42回水晶体研究会合同学会
  • Place of Presentation: 岩手県盛岡市、いわて県民情報交流センター アイーナ
  • Year and Date: 2016-07-29
• [Presentation] ヒト不死化角膜上皮細胞を用いた三次元角膜モデルの有用性． (2016)
  • Author(s): 山本直樹、平松範子、山下宏美、加藤義直、佐藤淳、中田悟、松井優子、真野陽介、原和宏、増藺夕紀子、中村政志、小島 肇
  • Organizer: 日本組織培養学会第89回大会
  • Place of Presentation: 大阪府大阪市、千里ライフサイエンスセンター
  • Year and Date: 2016-05-25
• [Presentation] DBA2-GFPマウス虹彩細胞由来新規iPS細胞の作出 (2015)
  • Author(s): 山本直樹、平松範子、大熊真人、宮地栄一、磯谷澄人、今泉和良、谷川篤宏、堀口正之、谷口孝喜
  • Organizer: 第47回藤田学園医学会
  • Place of Presentation: 愛知県、豊明市
  • Year and Date: 2015-10-01
• [Presentation] iPS細胞による再生医療へのアプローチ (2015)
  • Author(s): 平松範子、山本直樹、山下宏美、大熊真人、磯谷澄人、谷川篤宏、宮地栄一、堀口正之、今泉和良
  • Organizer: 第47回藤田学園医学会
  • Place of Presentation: 愛知県、豊明市
  • Year and Date: 2015-10-01
• [Presentation] 幹細胞を用いたさまざまな眼組織の再生 (2015)
  • Author(s): 山本直樹
  • Organizer: 第54回日本白内障学会・第41回水晶体研究会合同学会
  • Place of Presentation: 愛知県、名古屋市
  • Year and Date: 2015-09-18
  • Invited
• [Remarks] 藤田保健衛生大学研究支援推進センター共同利用研究施設
  • URL: http://www.fujita-hu.ac.jp/~kyoriken/research/reserachpage.html
• [Remarks] http://www.fujita-hu.ac.jp/~kyoriken/index.html