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Immunogenicity of iPS-derived retinal pigment epithelial (RPE) cells

Research Project

Project/Area Number 25293357
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Ophthalmology
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Sugita Sunao  国立研究開発法人理化学研究所, 多細胞システム形成研究センター, 副プロジェクトリーダー (10299456)

Project Period (FY) 2013-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2016: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2015: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2013: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
KeywordsiPS細胞 / 網膜色素上皮細胞 / MHC抗原 / 移植 / 拒絶反応 / 炎症細胞 / サイトカイン / 網膜 / 免疫
Outline of Final Research Achievements

We demonstrated experimentally that immune responses can be avoided when retinal pigment epithelial (RPE) cells generated from iPSCs derived from a MHC/HLA homozygous donor are matched with MHC/HLA of recipient. Our research team developed an in vivo experimental method in a primate model, in which they transplanted RPE cells derived from iPSCs from a MHC homozygote monkey into a different monkey (MHC-matched), and an in vitro experimental system using RPE cells derived from human iPSCs and co-cultured them with human immune cells. In vivo data, no signs of immune rejection were observed in recipients of MHC-matched grafts, and the sheet grafts survived for at least six months post-transplantation. Similarly, the matching of at least three HLA gene loci (HLA-A, HLA-B, and HLA-DRBI) between iPSCs-derived RPE cells and the donor immune cells was sufficient for preventing the trigger of an immune response in vitro. Our study was published in two separate papers in Stem Cell Reports.

Report

(5 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (39 results)

All 2017 2016 2015 2014 2013

All Journal Article (7 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 7 results,  Open Access: 5 results,  Acknowledgement Compliant: 6 results) Presentation (28 results) (of which Int'l Joint Research: 2 results,  Invited: 19 results) Book (4 results)

  • [Journal Article] Establishment of multiplex solid-phase strip PCR test for detection of 24 ocular infectious disease pathogens.2017

    • Author(s)
      Nakano S, Sugita S, Tomaru Y, Hono A, Nakamuro T, Kubota T, Takase H, Manabu M, Takahashi M, Shimizu N.
    • Journal Title

      Invest Ophthalmol Vis Sci

      Volume: 58 Issue: 3 Pages: 1553-1559

    • DOI

      10.1167/iovs.16-20556

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Lack of T Cell Response to iPSC-Derived Retinal Pigment Epithelial Cells from HLA Homozygous Donors.2016

    • Author(s)
      Sugita S, Iwasaki Y, Makabe K, Kimura T, Futagami T, Suegami S, Takahashi M.
    • Journal Title

      Stem Cell Reports

      Volume: 7 Issue: 4 Pages: 619-634

    • DOI

      10.1016/j.stemcr.2016.08.011

    • NAID

      120006223636

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Successful Transplantation of Retinal Pigment Epithelial Cells from MHC Homozygote iPSCs in MHC-Matched Models2016

    • Author(s)
      Sugita S, Iwasaki Y, Makabe K, Kamao H, Mandai M, Shiina T, Ogasawara K, Hirami Y, Kurimoto Y, Takahashi M
    • Journal Title

      Stem Cell Reports

      Volume: 11 Issue: 4 Pages: 635-648

    • DOI

      10.1016/j.stemcr.2016.08.010

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Differentiation/Purification Protocol for Retinal Pigment Epithelium from Mouse Induced Pluripotent Stem Cells as a Research Tool.2016

    • Author(s)
      Iwasaki Y, Sugita S, Mandai M, Yonemura S, Onishi A, Ito S, Mochizuki M, Ohno-Matsui K, Takahashi M.
    • Journal Title

      PLoS One

      Volume: 11 Issue: 7 Pages: e0158282-e0158282

    • DOI

      10.1371/journal.pone.0158282

    • NAID

      120006534981

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Inhibition of T-cell activation by retinal pigment epithelial cells derived from induced pluripotent stem cells.2015

    • Author(s)
      Sugita S, Kamao H, Iwasaki Y, Okamoto S, Hashiguchi T, Iseki K, Hayashi N, Mandai M, Takahashi M.
    • Journal Title

      Invest Ophthalmol Vis Sci.

      Volume: 56 Issue: 2 Pages: 1051-62

    • DOI

      10.1167/iovs.14-15619

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Protective effects of human iPS-derived retinal pigmented epithelial cells in comparison with human mesenchymal stromal cells and human neural stem cells on the degenerating retina in rd1 mice.2015

    • Author(s)
      Sun J, Mandai M, Kamao H, Hashiguchi T, Shikamura M, Kawamata S, Sugita S, Takahashi M.
    • Journal Title

      Stem Cells

      Volume: 33 Issue: 5 Pages: 1543-53

    • DOI

      10.1002/stem.1960

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Characterization of Human Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium Cell Sheets Aiming for Clinical Application2014

    • Author(s)
      Kamao H, Mandai M, Okamoto S, Sakai N, Suga A, Sugita S, Kiryu J, Takahashi M.
    • Journal Title

      Stem Cell Reports

      Volume: 2 Issue: 2 Pages: 205-218

    • DOI

      10.1016/j.stemcr.2013.12.007

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] iPS細胞関連網膜色素上皮移植の現状と今後の展望2017

    • Author(s)
      杉田 直
    • Organizer
      第9回Saitama Ophthalmology Free Talk Meeting
    • Place of Presentation
      サフレ埼玉(埼玉県・埼玉市)
    • Year and Date
      2017-03-04
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] iPS細胞を用いた眼科領域での臨床応用2016

    • Author(s)
      杉田 直
    • Organizer
      宮城眼科先進医療研究会
    • Place of Presentation
      東北大学(宮城県・仙台市)
    • Year and Date
      2016-12-08
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] RPE regulation of innate immune activity and functionality in macrophages - RPE cells differentiated from iPS cells possess immune functions similar to primary RPE cells2016

    • Author(s)
      Sunao Sugita
    • Organizer
      ISER2016
    • Place of Presentation
      京王プラザホテル(東京都・新宿区)
    • Year and Date
      2016-09-25
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] iPS細胞で眼炎症性疾患が治せるか?2016

    • Author(s)
      杉田 直
    • Organizer
      フォーサム 2016
    • Place of Presentation
      大阪国際会議場(大阪府・大阪市)府・大阪市)
    • Year and Date
      2016-07-01
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 網膜色素上皮iPS細胞移植の現状2016

    • Author(s)
      杉田 直
    • Organizer
      第120回日本眼科学会総会
    • Place of Presentation
      仙台国際会議場(宮城県・仙台市)
    • Year and Date
      2016-04-07
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] ぶどう膜炎におけるトランスレーショナルリサーチ - 網膜色素上皮iPS細胞移植の現状2016

    • Author(s)
      杉田 直
    • Organizer
      第120回日本眼科学会総会 4/7-10/2016
    • Place of Presentation
      仙台国際会議場(宮城県・仙台市)
    • Year and Date
      2016-04-07
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 加齢黄斑変性に対する自家iPS細胞由来網膜色素上皮細胞シート移植1年の臨床経過2016

    • Author(s)
      栗本康夫、平見恭彦、藤原雅史、森永千佳子、山本 翠、藤田佳奈子、杉田 直、万代道子、高橋政代
    • Organizer
      第15回日本再生医療学会
    • Place of Presentation
      大阪国際会議場(大阪府・大阪市)
    • Year and Date
      2016-03-17
    • Related Report
      2015 Annual Research Report
  • [Presentation] 細胞移植と免疫反応 - 網膜再生移植時の拒絶反応2016

    • Author(s)
      杉田 直
    • Organizer
      第15回日本再生医療学会
    • Place of Presentation
      大阪国際会議場(大阪府・大阪市)
    • Year and Date
      2016-03-17
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] iPS細胞と網膜再生医療について2016

    • Author(s)
      杉田 直
    • Organizer
      兵庫県職員薬剤師会総会総合研究会
    • Place of Presentation
      ホテルクラウンパ レス神戸(神戸)
    • Year and Date
      2016-03-01
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] iPS細胞由来網膜色素上皮細胞移植:臨床試験症例報告および今後の方針2015

    • Author(s)
      杉田 直
    • Organizer
      平成27年度久留米大学眼科同門会総会
    • Place of Presentation
      グランドハイアット福岡(福岡県・福岡市)
    • Year and Date
      2015-10-17
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] iPS細胞由来網膜色素上皮細胞の拒絶反応移植モデル解析2015

    • Author(s)
      杉田 直、岩崎優子、真壁健一、鎌尾浩行、万代道子、高橋政代
    • Organizer
      第36回日本再生・炎症学会
    • Place of Presentation
      東京
    • Year and Date
      2015-07-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] PS細胞由来網膜色素上皮細胞のin vivo拒絶反応移植動物モデル解析2015

    • Author(s)
      杉田 直、岩崎優子、真壁健一、鎌尾浩行、万代道子、高橋政代
    • Organizer
      第49回日本眼炎症学会(フォーサム大阪)
    • Place of Presentation
      大阪国際会議場(大阪府・大阪市)
    • Year and Date
      2015-07-10
    • Related Report
      2015 Annual Research Report
  • [Presentation] Failure of T-cell immune attack on iPS cells-derived retinal pigment epithelial cells from HLA homozygous donors.2015

    • Author(s)
      Sugita S, Iwasaki Y, Makabe K, Kamao H, Mandai M, Takahashi M.
    • Organizer
      ARVO
    • Place of Presentation
      Denver (USA)
    • Year and Date
      2015-05-03
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] iPS細胞由来網膜色素上皮細胞移植:ヒト臨床への取り組み2015

    • Author(s)
      杉田 直
    • Organizer
      第10回YOKOHAMA病診連携の会
    • Place of Presentation
      横浜(横浜グランドインターコンチネンタルホテル)
    • Year and Date
      2015-03-13
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] iPS細胞を用いた加齢黄斑変性の再生医療2014

    • Author(s)
      杉田 直
    • Organizer
      第30回西宮市ライフサイエンスセミナー
    • Place of Presentation
      西宮市(西宮市フレンテホール)
    • Year and Date
      2014-10-24
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] iPS細胞由来網膜色素上皮細胞移植: ヒト臨床試験への試み2014

    • Author(s)
      杉田 直
    • Organizer
      第22回OZAK会学術集会
    • Place of Presentation
      千葉市(幕張国際研修センター)
    • Year and Date
      2014-10-05
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] iPS細胞の網膜再生医療 -網膜変性疾患への臨床応用2014

    • Author(s)
      杉田 直
    • Organizer
      第42回日本臨床免疫学会総会
    • Place of Presentation
      東京(京王プラザホテル)
    • Year and Date
      2014-09-25
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] iPS細胞由来網膜色素上皮細胞のin vitro拒絶反応試験2014

    • Author(s)
      杉田 直、岩崎優子、高橋政代
    • Organizer
      第48回日本眼炎症学会
    • Place of Presentation
      東京(東京国際フォーラム)
    • Year and Date
      2014-07-04
    • Related Report
      2014 Annual Research Report
  • [Presentation] iPS細胞由来網膜色素上皮細胞の臨床試験:AMD患者網膜下移植2014

    • Author(s)
      杉田 直
    • Organizer
      第6回North Osaka Ophthalmology Seminar
    • Place of Presentation
      大阪(大阪国際会議場)
    • Year and Date
      2014-05-22
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] iPS細胞由来網膜色素上皮細胞移植:ヒト臨床試験および拒絶反応対策2014

    • Author(s)
      杉田 直
    • Organizer
      第67回栃木県眼科集談会
    • Place of Presentation
      栃木(自治医科大学地域医療情報研修センター)
    • Year and Date
      2014-05-11
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 免疫寛容研究の新しい展開 – 色素上皮由来の免疫寛容2014

    • Author(s)
      杉田 直
    • Organizer
      第118回日本眼科学会総会
    • Place of Presentation
      東京(東京国際フォーラム)
    • Year and Date
      2014-04-03
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] iPS細胞由来網膜色素上皮細胞のHLA発現変化2014

    • Author(s)
      杉田 直、岩崎優子、高橋政代
    • Organizer
      第118回日本眼科学会総会
    • Place of Presentation
      東京(東京国際フォーラム)
    • Year and Date
      2014-04-02
    • Related Report
      2014 Annual Research Report
  • [Presentation] iPS細胞由来網膜色素上皮細胞移植:臨床試験に向けた免疫原性・拒絶反応対策2014

    • Author(s)
      杉田 直
    • Organizer
      日本免疫治療学会(招待講演)
    • Place of Presentation
      東京(パレスホテル東京)
    • Year and Date
      2014-02-22
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] iPS細胞由来網膜色素上皮細胞 (RPE) の免疫原性解析2013

    • Author(s)
      杉田 直
    • Organizer
      第67回日本臨床眼科学会
    • Place of Presentation
      横浜(パシフィコ横浜)
    • Year and Date
      2013-10-31
    • Related Report
      2013 Annual Research Report
  • [Presentation] iPS細胞由来網膜色素上皮細胞の免疫抑制能解析2013

    • Author(s)
      杉田 直、高橋政代
    • Organizer
      フォーサム大阪
    • Place of Presentation
      大阪(大阪国際会議場)
    • Year and Date
      2013-07-12
    • Related Report
      2013 Annual Research Report
  • [Presentation] Retinal pigment epithelial cells (RPE) induced from induced pluripotent stem (iPS) cells inhibit activation of T cells in vitro2013

    • Author(s)
      Sugita S, Takahashi M.
    • Organizer
      ARVO (The Association for Research in Vision and Ophthalmology)
    • Place of Presentation
      Seattle, Washington (USA)
    • Year and Date
      2013-05-05
    • Related Report
      2013 Annual Research Report
  • [Presentation] iPS細胞由来の網膜細胞移植で視覚障害者を救えるか?2013

    • Author(s)
      杉田 直
    • Organizer
      第67回佐野市民病院市民講座(招待講演)
    • Place of Presentation
      栃木県佐野市(佐野市民病院)
    • Year and Date
      2013-04-19
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 網膜色素上皮移植の免疫原性解析2013

    • Author(s)
      杉田 直
    • Organizer
      第117回日本眼科学会総会(招待講演)
    • Place of Presentation
      東京(東京国際フォーラム)
    • Year and Date
      2013-04-04
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Book] 月刊糖尿病: iPS細胞を用いた網膜疾患に対する再生医療開発2016

    • Author(s)
      杉田 直
    • Total Pages
      8
    • Publisher
      医学出版
    • Related Report
      2016 Annual Research Report
  • [Book] 炎症と免疫: iPS細胞を用いた難治性眼疾患の治療戦略2015

    • Author(s)
      杉田 直
    • Total Pages
      6
    • Publisher
      先端医学社
    • Related Report
      2015 Annual Research Report
  • [Book] 再生医療の臨床応用: 網膜変性疾患への臨床応用2015

    • Author(s)
      杉田 直
    • Total Pages
      5
    • Publisher
      日本臨床免疫学会会誌
    • Related Report
      2015 Annual Research Report
  • [Book] 再生医療の最新の進歩: iPS細胞を用いた網膜再生 - ヒトiPS細胞由来網膜色素上皮細胞の臨床応用2014

    • Author(s)
      杉田 直 高橋政代
    • Total Pages
      10
    • Publisher
      最新医学社
    • Related Report
      2014 Annual Research Report

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Published: 2013-05-21   Modified: 2018-03-22  

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