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2011 Fiscal Year Final Research Report

Mechanism of regeneration of renal tubular cells and differentiation from ES and iPS cells to renal tubular cells

Research Project

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Project/Area Number 21591038
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Kidney internal medicine
Research InstitutionKeio University

Principal Investigator

MONKAWA Toshiaki  慶應義塾大学, 医学部, 講師 (80286484)

Project Period (FY) 2009 – 2011
Keywords腎臓 / 尿細管 / 再生医学 / ES細胞 / iPS細胞
Research Abstract

The S3 segment of the kidney proximal tubule is highly susceptible to ischemia insults but has a remarkable capacity to repair its structure and function. By applying the "toxin receptor mediated cell knockout" method under the control of the S3 segment-specific promoter Gsl5, we established a transgenic mouse line expressing the human diphtheria toxin(DT) receptor only in the S3 segment. The administration of DT to these transgenic mice caused the selective ablation of S3 segment cells in a dose-dependent manner. These results indicate that this transgenic mouse can suffer acute kidney injury(AKI) caused by S3 segment-specific damage after DT administration. This transgenic line offers an excellent model to uncover the mechanisms of AKI and its rapid recovery.
We tried to establish differentiation method of ES cells and iPS cells into renal tubular cells. In ES cells, Activin enhanced the differentiation of ES cells to tubular cells, judging by expression of Ksp-Cadherin, the epithelial marker. Activin also enhanced the differentiation of iPS cells to tubular cells, although the enhancement was lower than in ES cells. We generated monoclonal antibody against the extracellular domain of Ksp-Cadherin. Flow cytometry using the antibody purified the Ksp-positive cells, which formed tubular structure on Matrigel. We established the differentiation method of ES and iPS cells into renal tubular cells.

  • Research Products

    (8 results)

All 2012 2011 2009

All Journal Article (3 results) (of which Peer Reviewed: 3 results) Presentation (4 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Selective depletion of mouse kidney proximal straight tubule cells causes acute kidney injury2012

    • Author(s)
      Sekine M, Monkawa T, Morizane R, Matsuoka K, Taya C, Akita Y, Joh K, Itoh H, Hayashi M, Kikkawa Y, Kohno K, Suzuki A, Yonekawa H.
    • Journal Title

      Transgenic Res

      Volume: 21 Pages: 51-62

    • Peer Reviewed
  • [Journal Article] The role of microRNA-145 in human embryonic stem cell differentiation into vascular cells2011

    • Author(s)
      Yamaguchi S, Yamahara K, Homma K, Suzuki S, Fujii S, Morizane R, Monkawa T, Matsuzaki Y, Kangawa K, Itoh H
    • Journal Title

      Atherosclerosis

      Volume: 219 Pages: 468-474

    • Peer Reviewed
  • [Journal Article] Differentiation of murine embryonic stem and induced pluripotent stem cells to renal lineage in vitro2009

    • Author(s)
      Morizane R, Monkawa T, Itoh H.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 390 Pages: 1334-1339

    • Peer Reviewed
  • [Presentation] Purification of differentiated tubular cells from mouse embryonic stem cells using flow cytometry2011

    • Author(s)
      Morizane R, Monkawa T, Itoh H
    • Organizer
      第44回米国腎臓学会
    • Place of Presentation
      米国フィラデルフィア
    • Year and Date
      2011-11-10
  • [Presentation] 尿細管細胞の上皮間葉移行に関与するmiRNAの検討(miRNA involved with epithelial-mesenchymal transition of renal tubular cell)2011

    • Author(s)
      森實隆司、門川俊明、山口慎太郎、伊藤裕
    • Organizer
      第54回日本腎臓学会学術総会
    • Place of Presentation
      日本、横浜
    • Year and Date
      2011-06-17
  • [Presentation] Activin enhances differentiation of mouse ES cell to tubule cell2009

    • Author(s)
      Morizane R, Monkawa T, Itoh H
    • Organizer
      第42回米国腎臓学会
    • Place of Presentation
      米国サンディエゴ
    • Year and Date
      2009-10-31
  • [Presentation] マウスES細胞を用いた腎構成細胞への分化誘導(Differentiation to renal cell lineage from mouse ES cell)2009

    • Author(s)
      森實隆司、門川俊明、西崇彦、伊藤裕
    • Organizer
      第52回日本腎臓学会学術総会
    • Place of Presentation
      日本、横浜
    • Year and Date
      2009-06-03
  • [Patent(Industrial Property Rights)] 抗KSPマウスモノクローナル抗体を用いた、胚性幹細胞からin vitroでの腎構成細胞の誘導方法の開発2011

    • Inventor(s)
      森實隆司、門川俊明、伊藤裕
    • Industrial Property Rights Holder
      慶應義塾大学
    • Industrial Property Number
      特願、2011-209792
    • Filing Date
      2011-09-26

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Published: 2013-07-31  

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