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Cell therapy using human pluripotent stem cell-derived erythropoietin-producing cells improves renal anemia

Research Project

Project/Area Number 15K09266
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Kidney internal medicine
Research InstitutionKagawa University

Principal Investigator

Hitomi Hirofumi  香川大学, 医学部, 准教授 (70346641)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords再生医学 / 移植・再生医療 / iPS細胞 / エリスロポエチン / 腎性貧血
Outline of Final Research Achievements

We established a method to generate erythropoietin (EPO)-producing cells from human induced pluripotent stem cells (hiPSCs) by modifying previously reported hepatic differentiation protocols. These cells showed increased EPO expression and secretion in response to low oxygen conditions, prolyl hydroxylase domain-containing enzymes inhibitors or insulin-like growth factor-1. The EPO protein secreted from hiPSC-derived EPO-producing cells (hiPSC-EPO cells) induced the erythropoietic differentiation of umbilical cord blood progenitors in vitro. Furthermore, transplantation of hiPSC-EPO cells improved renal anemia in adenine-induced CKD mice. In conclusion, hiPSC-EPO cells may be a useful tool for clarifying the mechanisms of EPO production and provide a novel therapeutic agent for anemia.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (38 results)

All 2017 2016 2015 2014

All Journal Article (11 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 11 results,  Open Access: 2 results,  Acknowledgement Compliant: 2 results) Presentation (27 results) (of which Int'l Joint Research: 2 results,  Invited: 3 results)

  • [Journal Article] Human pluripotent stem cell-derived erythropoietin-producing cells ameliorate renal anemia in mice2017

    • Author(s)
      Hitomi Hirofumi、Kasahara Tomoko、Katagiri Naoko、Hoshina Azusa、Mae Shin-Ichi、Kotaka Maki、Toyohara Takafumi、Rahman Asadur、Nakano Daisuke、Niwa Akira、Saito Megumu K.、Nakahata Tatsutoshi、Nishiyama Akira、Osafune Kenji
    • Journal Title

      Science Translational Medicine

      Volume: 9 Issue: 409

    • DOI

      10.1126/scitranslmed.aaj2300

    • NAID

      120006349331

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of a selective SGLT2 inhibitor, luseogliflozin, on circadian rhythm of sympathetic nervous function and locomotor activities in metabolic syndrome rats.2017

    • Author(s)
      Rahman A, Fujisawa Y, Nakano D, Hitomi H, Nishiyama A.
    • Journal Title

      Clin Exp Pharmacol Physiol.

      Volume: 44(4) Issue: 4 Pages: 522-525

    • DOI

      10.1111/1440-1681.12725

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Cardioprotective effects of SGLT2 inhibitors are possibly associated with normalization of the circadian rhythm of blood pressure2017

    • Author(s)
      Rahman Asadur、Hitomi Hirofumi、Nishiyama Akira
    • Journal Title

      Hypertension Research

      Volume: 40 Issue: 6 Pages: 535-540

    • DOI

      10.1038/hr.2016.193

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] How should we treat patients with primary aldosteronism to prevent new-onset diabetes mellitus?2017

    • Author(s)
      Hitomi Hirofumi、Nishiyama Akira
    • Journal Title

      J Hypertens

      Volume: 35 Issue: 8 Pages: 1575-1576

    • DOI

      10.1097/hjh.0000000000001440

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] IBMX protects human proximal tubular epithelial cells from hypoxic stress through suppressing hypoxia-inducible factor-1α expression2017

    • Author(s)
      Hasan Arif Ul、Kittikulsuth Wararat、Yamaguchi Fuminori、Musarrat Ansary Tuba、Rahman Asadur、Shibayama Yuki、Nakano Daisuke、Hitomi Hirofumi、Tokuda Masaaki、Nishiyama Akira
    • Journal Title

      Experimental Cell Research

      Volume: 358 Issue: 2 Pages: 343-351

    • DOI

      10.1016/j.yexcr.2017.07.007

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Responses of renal hemodynamics and tubular functions to acute sodium-glucose cotransporter 2 inhibitor administration in non-diabetic anesthetized rats2017

    • Author(s)
      Ansary Tuba M.、Fujisawa Yoshihide、Rahman Asadur、Nakano Daisuke、Hitomi Hirofumi、Kobara Hideki、Masaki Tsutomu、Titze Jens M.、Kitada Kento、Nishiyama Akira
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 9555-9555

    • DOI

      10.1038/s41598-017-09352-5

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A protease-activated receptor-1 antagonist protects against podocyte injury in a mouse model of nephropathy2017

    • Author(s)
      Guan Yu、Nakano Daisuke、Zhang Yifan、Li Lei、Liu Wenhua、Nishida Motohiro、Kuwabara Takashige、Morishita Asahiro、Hitomi Hirofumi、Mori Kiyoshi、Mukoyama Masashi、Masaki Tsutomu、Hirano Katsuya、Nishiyama Akira
    • Journal Title

      J Pharmacol Sci

      Volume: 135 Issue: 2 Pages: 81-88

    • DOI

      10.1016/j.jphs.2017.09.002

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Hormonal changes following a low-salt diet in patients with Ménière's disease.2016

    • Author(s)
      Miyashita T, Inamoto R, Fukuda S, Hoshikawa H, Hitomi H, Kiyomoto H, Nishiyama A, Mori N.
    • Journal Title

      Auris Nasus Larynx

      Volume: 未定 Issue: 1 Pages: 52-57

    • DOI

      10.1016/j.anl.2016.03.001

    • NAID

      130006086011

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Effects of diuretics on sodium-dependent glucose cotransporter 2 inhibitor-induced changes in blood pressure in obese rats suffering from the metabolic syndrome.2016

    • Author(s)
      Rahman A, Kittikulsuth W, Fujisawa Y, Sufiun A, Rafiq K, Hitomi H, Nakano D, Sohara E, Uchida S, Nishiyama A.
    • Journal Title

      J Hypertens.

      Volume: 34 Issue: 5 Pages: 893-906

    • DOI

      10.1097/hjh.0000000000000871

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Urinary Angiotensinogen Could Be a Prognostic Marker of the Renoprotection of Olmesartan in Metabolic Syndrome Patients.2016

    • Author(s)
      Mizushige T, Kobori H, Hitomi H, Nishijima Y, Tomoda F, Morimoto S, Kohno M, Nishiyama A.
    • Journal Title

      Int J Mol Sci

      Volume: 17 Issue: 11 Pages: 1800-1800

    • DOI

      10.3390/ijms17111800

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Chelation of dietary iron prevents iron accumulation and macrophage infiltration in the type I diabetic kidney.2014

    • Author(s)
      Morita T, Nakano D, Kitada K, Morimoto S, Ichihara A, Hitomi H, Kobori H, Shiojima I, Nishiyama A.
    • Journal Title

      Eur J Pharmacol.

      Volume: 756 Pages: 85-91

    • DOI

      10.1016/j.ejphar.2015.03.053

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] Esaxerenone (CS-3150), a non-steroidal selective mineralocorticoid receptor antagonist, elicits renoprotective effects in high salt-treated type 2 diabetic KKAy mice2017

    • Author(s)
      Nishiyama A, Hitomi H, Nakano D.
    • Organizer
      World Congress of Nephrology 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] SGLT2阻害薬の腎循環・機能に及ぼす直接的な影響2017

    • Author(s)
      西山 成、藤澤良秀、ラフマンアサダ、中野大介、人見浩史、北田研人、アンサリーチュバ
    • Organizer
      第7回日本腎臓リハビリーテーション学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] AKIに伴って発症するCKDに対するSGLT2阻害薬の抑制効果2017

    • Author(s)
      西山 成、中野大介、人見浩史、Yifan Z
    • Organizer
      第29回腎と脂質研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 腎虚血再灌流後に生じる慢性間質線維化におけるSGLT2阻害薬の予防効果2017

    • Author(s)
      西山 成、中野大介、人見浩史
    • Organizer
      第54回日本臨床分子医学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Effects of SGLT-2 Inhibitor and angiotensin Ⅱ receptor blocker on renin-angiotensin system in subtotal nephrectomized rats.2017

    • Author(s)
      Li L、Konishi Y、Morikawa T、Nakano D、 Hitomi H、 Nishiyama A
    • Organizer
      第60回日本腎臓学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Protease-activated receptor-1 antagonist protects the doxorubicin-induced podocyte injury in mice.2017

    • Author(s)
      Guan Y、Nakano D、Hitomi H、Nishiyama A
    • Organizer
      第60回日本腎臓学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Responses of arterial pressure to high salt intake in adenineinduced chronic kidney disease rats.2017

    • Author(s)
      Wan N、Fujisawa Y、Rahman A、Nakano D、Hitomi H、Nishiyama A
    • Organizer
      第60回日本腎臓学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 糖尿病マウスにおける新規非ステロイド性ミネラロコルチコイド受容体拮抗薬エサキセレノンの腎保護効果2017

    • Author(s)
      西山 成、中野大介、人見浩史、ラフィカジ
    • Organizer
      第60回日本腎臓学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Proteinase-activated receptor-1 はポドサイト障害によるアルブミン尿の病態に関与する2017

    • Author(s)
      Guan Y、中野大介、人見浩史、平野勝也、西山 成
    • Organizer
      第17回日本NO学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Proteinase-activated receptor-1阻害による腎保護2017

    • Author(s)
      Guan Y、中野大介、Liu W、Yifan Z、Lei L、人見浩史、平野勝也、西山 成
    • Organizer
      第131回日本薬理学会近畿部会
    • Related Report
      2017 Annual Research Report
  • [Presentation] SGLT2阻害薬は急性腎障害後に生じる線維化を予防する2017

    • Author(s)
      西山 成、中野大介、人見浩史、張 一凡
    • Organizer
      第17回日本抗加齢医学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] メタボリックシンドロームラットにおけるSGLT2阻害薬の交感神経と自発連動に対する影響2017

    • Author(s)
      西山 成、藤澤良秀、中野大介、人見浩史、ラフマンアサダ
    • Organizer
      第17回日本抗加齢医学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 腎ポドサイト障害進展におけるProteinase-activated receptor-1の関与2017

    • Author(s)
      中野大介、Guan Y、Liu W、張 一凡、Li L、人見浩史、平野勝也、西山 成
    • Organizer
      第44回日本毒性学会学術年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] iPS細胞を用いたエリスロポエチン産生細胞による腎性貧血に対する細胞療法の検討2017

    • Author(s)
      人見浩史、長船健二、西山 成
    • Organizer
      第2回黒潮カンファレンス
    • Related Report
      2017 Annual Research Report
  • [Presentation] Responses of Blood Pressure and Sympathetic Nerve Activity to High Salt in Adeninetreated CKD Rats2017

    • Author(s)
      Wan N、Fujisawa Y、Nakano D、Hitomi H、Nishiyama A.
    • Organizer
      第40回日本高血圧学会総会
    • Related Report
      2017 Annual Research Report
  • [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の検討2017

    • Author(s)
      人見浩史、中野大介、長船健二、西山成
    • Organizer
      第40回日本高血圧学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Effects of the Selective Chymase Inhibitor, TEI-F00806, on Intrarenal Renin-angiotensin System in Salt-treated Angiotensin I-infused Hypertensive Mice.2017

    • Author(s)
      Ansary T、Fujisawa Y、Urushihara M、Nagata S、Urata H、Nakano D、Hitomi H、Kagami A、Nishiyama A
    • Organizer
      第40回日本高血圧学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Effects of An SGLT2 Inhibitor on the Systemic and Renin Angiotensin System in Subtotally Nephrectomized Rats.2017

    • Author(s)
      Li L、Konishi Y、Morikawa T、Kitabayashi C、Nakano D、Hitomi H、Kobori H、Nishiyama A.
    • Organizer
      第40回日本高血圧学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Responses of arterial pressure and sympathetic nerve activity to high salt intake in adenine-treated CKD rats.2017

    • Author(s)
      Wan N、Fujisawa Y、Rahman A、Nakano D、Hitomi H、Nishiyama A
    • Organizer
      第53回高血圧関連疾患モデル学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 新規非ステロイド性選択的ミネラロコルチコイド受容体拮抗薬エサキセレノンの薬効評価:高食塩投与2型糖尿病KKAyマウスにおける降圧・腎保護作用2017

    • Author(s)
      Lei L、中野大介、人見浩史、西山 成
    • Organizer
      第53回高血圧関連疾患モデル学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Effect of a SGLT2 inhibitor on activity of systemic and intrarenal renin-angiotensin system in subtotally nephrectomized rats.2017

    • Author(s)
      Lei L、中野大介、人見浩史、小堀浩幸、西山 成
    • Organizer
      第53回高血圧関連疾患モデル学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] iPS 細胞から分化誘導した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の検討2017

    • Author(s)
      人見 浩史、中野 大介、長船 健二、西山 成
    • Organizer
      第27回日本循環薬理学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] iPS細胞実験の現状と可能性.2016

    • Author(s)
      人見浩史
    • Organizer
      第39回日本高血圧学会総会
    • Place of Presentation
      宮城県仙台市
    • Year and Date
      2016-09-30
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] Establishment of a mouse model of renal anemia.2016

    • Author(s)
      Rahman A, Kitada K, Hitomi H, Nakano D, Nishiyama A.
    • Organizer
      The 17th International SHR Symposium
    • Place of Presentation
      Tokyo, Japan
    • Year and Date
      2016-09-22
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] エリスロポエチン産生細胞による新しい治療の試み2015

    • Author(s)
      西山 成、人見浩史、長船健二
    • Organizer
      第53回日本人工臓器学会大会
    • Place of Presentation
      東京都文京区
    • Year and Date
      2015-11-19
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] iPS細胞をもちいたCKD貧血治療法の開発2015

    • Author(s)
      西山 成、人見浩史、長船健二
    • Organizer
      第23回クリニカルファーマシーシンポジウム
    • Place of Presentation
      愛知県名古屋市
    • Year and Date
      2015-07-04
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] ヒトiPS細胞由来EPO産生細胞を用いた腎性貧血に対する細胞療法の開発2015

    • Author(s)
      人見浩史、笠原朋子、保科あずさ、前 伸一、豊原敬文、小高真希、丹羽 明、Rahman A、中野大介、人見浩史、小堀浩幸、齋藤 潤、中畑龍俊、西山 成、長船健二
    • Organizer
      第58回日本腎臓学会学術総会
    • Place of Presentation
      愛知県名古屋市
    • Year and Date
      2015-06-05
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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