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Attempt to Regenerate Aging Kidneys Using a Renal Tubule Regeneration System Utilizing Renal Stem Cells

Research Project

Project/Area Number 20K08596
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

MAESHIMA AKITO  埼玉医科大学, 医学部, 教授 (70431707)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords尿細管再生 / 腎幹細胞 / 急性腎障害
Outline of Research at the Start

急性腎障害後の尿細管再生能力は加齢とともに低下し、高齢者では腎機能が回復せず透析導入に至るケースも少なくない。最近我々はその要因として「加齢に伴う腎幹細胞数の減少」を明らかにした。本研究では「腎幹細胞を起点とする尿細管再生システム」を利用した「加齢腎の再生」を試みる。Doxycycline誘導Histone 2B-GFPマウスを用いて、腎幹細胞をGFP標識し、腎幹細胞特異的に発現しているリガンド・受容体を探索する。腎幹細胞活性化因子を同定し、高齢マウスの腎幹細胞を増やすことができるかを検証する。本研究で得られた知見は、高齢者腎不全を減らすための腎再生医療の進歩に大きく貢献するものと思われる。

Outline of Final Research Achievements

In this study, we analyzed the proliferation and differentiation patterns of renal stem cells using Doxycycline-induced Histone 2B-GFP mice. By labeling the slowly dividing renal stem cells with GFP, we found that the number of GFP-positive tubular cells increased proportionally during the Doxycycline administration period, while it decreased inversely during the follow-up period. Based on these results, it was revealed that tubular cells that actively proliferate (regenerate) after renal injury also undergo slow division under normal conditions. By further elucidating the proliferation and differentiation patterns of renal stem cells using this mouse model, it is believed that the realization of renal regenerative medicine utilizing a "urinary tubule regeneration system based on renal stem cells" becomes possible.

Academic Significance and Societal Importance of the Research Achievements

本研究の成果は「腎幹細胞を起点とする尿細管再生システム」を利用した「腎再生医療」の確立に大きく貢献するものと思われる。内在する腎幹細胞を活性化し、腎臓が本来有している再生能力を最大限発揮させることにより、腎疾患の原因によらず腎機能が低下した症例に対して、「腎幹細胞を起点とする尿細管再生システム」を基盤とした「腎再生医療」が可能になる。また、加齢により失われた腎幹細胞を増加させて、尿細管再生システムを再び活性化することができれば、高齢者腎不全あるいは透析導入患者数の減少につながることが期待できると思われる。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (7 results)

All 2023 2022 2021

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 1 results) Presentation (3 results)

  • [Journal Article] Tubule-Derived Follistatin Is Increased in the Urine of Rats with Renal Ischemia and Reflects the Severity of Acute Tubular Damage2023

    • Author(s)
      Nagayama Izumi、Takayanagi Kaori、Hasegawa Hajime、Maeshima Akito
    • Journal Title

      Cells

      Volume: 12 Issue: 5 Pages: 801-801

    • DOI

      10.3390/cells12050801

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Initiation of renin?angiotensin system inhibitors and first complete remission in patients with primary nephrotic syndrome: a nationwide cohort study2023

    • Author(s)
      Shimizu Sayaka、et al.
    • Journal Title

      Clinical and Experimental Nephrology

      Volume: 27 Issue: 5 Pages: 480-489

    • DOI

      10.1007/s10157-023-02331-3

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Urinary Activin A: A Novel Biomarker for Human Acute Kidney Injury2022

    • Author(s)
      Nagayama Izumi、Maeshima Akito、Nagata Daisuke
    • Journal Title

      Diagnostics

      Volume: 12 Issue: 3 Pages: 661-661

    • DOI

      10.3390/diagnostics12030661

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Time to remission of proteinuria and incidence of relapse in patients with steroid-sensitive minimal change disease and focal segmental glomerulosclerosis: the Japan Nephrotic Syndrome Cohort Study2021

    • Author(s)
      Watanabe-Kusunoki K, Nakazawa D, Yamamoto J, Matsuoka N, Kaneshima N, Nakagaki T, Yamamoto R, Maoka T, Iwasaki S, Tsuji T, Fukasawa Y, Nishimoto N, Nishio S, Atsumi T
    • Journal Title

      Medicine (Baltimore)

      Volume: 35 Issue: 4 Pages: 1135

    • DOI

      10.1007/s40620-022-01279-z

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Presentation] 尿中Uromodulin:急性腎障害の回復を反映する新規バイオマーカー2022

    • Author(s)
      岩下山連,永山泉,大野和寿,長田太助,長谷川元,前嶋明人
    • Organizer
      第65回日本腎臓学会学術総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 症候性の低K血症、低Mg血症、低Ca血症を呈した慢性アルコール多飲患者の一例2022

    • Author(s)
      澤田衣里香,河合雄一郎,佐藤真理子,清水泰輔,田山陽資,小川智也,前嶋明人,長谷川元
    • Organizer
      第52回日本腎臓学会東部学術大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] IgA腎症の長期予後予測因子としての尿中アクチビンの有用性の検討2022

    • Author(s)
      池内秀和,前嶋明人,諏訪絢也,渡辺光治,中里見征央,浜谷博子,坂入徹,金子和光,廣村桂樹
    • Organizer
      第65回日本腎臓学会学術総会
    • Related Report
      2022 Annual Research Report

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Published: 2020-04-28   Modified: 2024-01-30  

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