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Novel therapy for renal anemia using human iPS cells

Research Project

Project/Area Number 18K08246
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53040:Nephrology-related
Research InstitutionKansai Medical University

Principal Investigator

HITOMI Hirofumi  関西医科大学, 医学部, 教授 (70346641)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords再生医学 / iPS細胞 / 移植・再生医療 / エリスロポエチン / 腎性貧血 / 薬効評価 / 細胞療法 / レチノイン酸
Outline of Final Research Achievements

Erythropoietin dysregulation is a hallmark of renal anemia. Although recombinant erythropoietin is beneficial and safe, more physiological therapies are required. We developed a differentiation protocol for erythropoietin-producing cells from human iPS cells. These cells produced and secreted functional erythropoietin protein. In addition, transplantation of these cells into a mouse model improved renal anemia. From the perspective of basic research, these cells may be a useful tool for investigating the molecular mechanisms of erythropoietin production and secretion. From the perspective of clinical research, these results may provide a physiological therapeutic agent for renal anemia.

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、腎性貧血の治療に対する安価でより生理的な管理を可能とする医療技術の向上に加え、貧血に対する新規治療法の開発による本邦の医薬産業界の活性化をもたらすものである。これまでヒトiPS細胞を用いた再生医療の試みがなされているが、エリスロポエチン産生細胞に関しては我々以外の報告は存在せず、本研究は全く新規で独自のものである。患者自身の体細胞から樹立され、ほぼ無限に増殖する能力を有する多能性幹細胞であるiPS細胞を用いることで、免疫抑制の必要ないエリスロポエチン産生細胞を大量に作製することも可能であり、今後も需要の増す腎性貧血治療に対して有効な手段になりうる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (20 results)

All 2021 2019 2018

All Journal Article (8 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 8 results,  Open Access: 5 results) Presentation (11 results) (of which Int'l Joint Research: 3 results,  Invited: 6 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Retinoic acid regulates erythropoietin production cooperatively with hypoxia-inducible factors in human iPSC-derived erythropoietin-producing cells2021

    • Author(s)
      Katagiri Naoko、Hitomi Hirofumi、Mae Shin-Ichi、Kotaka Maki、Lei Li、Yamamoto Takuya、Nishiyama Akira、Osafune Kenji
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 3936-3936

    • DOI

      10.1038/s41598-021-83431-6

    • NAID

      120006960306

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CD140b and CD73 are markers for human induced pluripotent stem cell‐derived erythropoietin‐producing cells2019

    • Author(s)
      Nishimoto S, Mizuno T, Naagamatsu T. et al.
    • Journal Title

      FEBS Open Bio

      Volume: 10 Issue: 3 Pages: 427-433

    • DOI

      10.1002/2211-5463.12800

    • NAID

      120006879490

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Failure to confirm an SGLT2 inhibitor-induced hematopoietic effect in non-diabetic rats with renal anemia.2019

    • Author(s)
      Yamazaki D, Konishi Y, Morikawa T, Kobara H, Masaki T, Hitomi H, Osafune K, Nakano D, Kittikulsuth W, Nishiyama A.
    • Journal Title

      J Diabetes Investig

      Volume: in press Issue: 4 Pages: 834-843

    • DOI

      10.1111/jdi.13205

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A novel approach to adenine-induced chronic kidney disease associated anemia in rodents.2018

    • Author(s)
      Rahman A, Yamazaki D, Sufiun A, Kitada K, Hitomi H, Nakano D, Nishiyama A.
    • Journal Title

      PLoS One

      Volume: 13 Issue: 2 Pages: e0192531-e0192531

    • DOI

      10.1371/journal.pone.0192531

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effects of an SGLT2 inhibitor on the systemic and intrarenal renin-angiotensin system in subtotally nephrectomized rats.2018

    • Author(s)
      Li L, Konishi Y, Morikawa T, Zhang Y, Kitabayashi C, Kobara H, Masaki T, Nakano D, Hitomi H, Kobori H, Nishiyama A.
    • Journal Title

      J. Pharmacol. Sci.

      Volume: 137 Issue: 2 Pages: 220-223

    • DOI

      10.1016/j.jphs.2017.10.006

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A sodium-glucose cotransporter 2 inhibitor attenuates renal capillary injury and fibrosis by a vascular endothelial growth factor-dependent pathway after renal injury in mice.2018

    • Author(s)
      Zhang Y, Nakano D, Guan Y, Hitomi H, Uemura A, Masaki T, Kobara H, Sugaya T, Nishiyama A.
    • Journal Title

      Kidney Int

      Volume: 94 Issue: 3 Pages: 524-535

    • DOI

      10.1016/j.kint.2018.05.002

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Sympathetic Nervous Activity.2018

    • Author(s)
      Wan N, Rahman A, Hitomi H, Nishiyama A.
    • Journal Title

      Front Endocrinol

      Volume: 26 Pages: 421-421

    • DOI

      10.3389/fendo.2018.00421

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hypertension with diabetes mellitus “Complications”.2018

    • Author(s)
      Yamazaki D, Hitomi H, Nishiyama A.
    • Journal Title

      Hypertens Res

      Volume: 41 Issue: 3 Pages: 147-156

    • DOI

      10.1038/s41440-017-0008-y

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] iPS細胞を用いた腎臓病における臨床応用と研究の展望2021

    • Author(s)
      人見浩史
    • Organizer
      第57回近畿小児腎臓病研究会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] iPS細胞由来細胞を用いた腎臓・内分泌領域創薬の新展開2019

    • Author(s)
      人見浩史
    • Organizer
      第92回日本薬理学会年会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] CRISPR/Cas9 システムを用いたヒト造血幹細胞におけるCD34抗原の発現意義の解析2019

    • Author(s)
      松岡由和, 角出啓輔, 中塚隆介, 白水泰昌, 藤岡龍哉, 薗田精昭, 服部文幸, 人見浩史
    • Organizer
      第18回日本再生医療学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 腎疾患におけるiPS細胞の臨床応用2019

    • Author(s)
      人見浩史
    • Organizer
      第54回日本小児腎臓病学会学術集会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] iPS細胞を用いた腎性貧血および内分泌疾患治療の展望2019

    • Author(s)
      人見浩史
    • Organizer
      第64回日本透析医学会総会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Human pluripotent stem cell-derived erythropoietin-producing cells improve renal anemia in mice2018

    • Author(s)
      Hitomi H, Nakano D, Osafune K, Nishiyama A
    • Organizer
      18th World Congress of Basic and Clinical Pharmacology (WCP2018) Kyoto
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Human pluripotent stem cell-derived erythropoietin-producing cells improve renal anemia in mice2018

    • Author(s)
      Hitomi H, Kasahara T, Katagiri N, Hoshina A, Mae S, Kotaka M, Toyohara T, Rahman A, Nakano D, Niwa A, Saito M, Nakahata T, Nishiyama A, Osafune K
    • Organizer
      ISSCR 2018 Annual Meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] iPS細胞を用いて腎性貧血を治療する2018

    • Author(s)
      人見浩史, 西山成, 長船健二
    • Organizer
      第63回日本透析医学会学術集会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] iPS細胞由来エリスロポエチン産生細胞を用いた腎性貧血に対する細胞療法開発2018

    • Author(s)
      人見浩史, 笠原朋子, 片桐直子, 保科あずさ, 前伸一, 小髙真希, 豊原敬文, Asadur Rahman, 中野大介, 丹羽明, 斎藤潤, 中畑龍俊, 西山成, 長船健二
    • Organizer
      第61回日本腎臓学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Human pluripotent stem cell-derived erythropoietin-producing cells ameliorate renal anemia in mice.2018

    • Author(s)
      Hitomi H, Nishiyama A, Osafune K
    • Organizer
      ISN Frontiers meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] iPS細胞を用いた慢性腎不全の次世代治療法-腎性貧血細胞治療の可能性2018

    • Author(s)
      人見浩史、西山成、長船健二
    • Organizer
      第48回日本腎臓学会西部学術大会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Patent(Industrial Property Rights)] 多能性幹細胞から腹膜中皮細胞を分化誘導する方法2021

    • Inventor(s)
      加藤憲、人見浩史
    • Industrial Property Rights Holder
      加藤憲、人見浩史
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2021-028107
    • Filing Date
      2021
    • Related Report
      2020 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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