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Developing the differentiation methods from pluripotent stem cells to glomerular endothelial cells for diabetic research

Research Project

Project/Area Number 19K23933
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0902:General internal medicine and related fields
Research InstitutionTohoku University

Principal Investigator

Toyohara Takafumi  東北大学, 医工学研究科, 特任助教 (60594182)

Project Period (FY) 2019-08-30 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords内皮細胞 / iPS細胞 / 腎臓 / 糸球体 / ES細胞 / 多能性幹細胞 / 糖尿病
Outline of Research at the Start

糖尿病による腎障害に対する有効な治療法は未だ開発されていない。糖尿病性腎症発症において早期に機能不全に陥る細胞の一つとして糸球体内皮細胞が知られているが糸球体内皮細胞に機能不全が生じるメカニズムについては十分に解明されていない。そこで本研究ではヒトの様々な細胞に分化できるヒト多能性幹細胞からヒト糸球体内皮細胞を作製し、糖尿病性腎症のにおける糸球体内皮障害の解明と治療開発を促進することを目的とする。

Outline of Final Research Achievements

In this project, we aimed to establish differentiation methods from pluripotent stem cells to glomerular endothelial cells for developing new therapy against diabetic nephropathy. We screened some growth factors existing at glomerulus that increase the expression of DKK2, one of the potential markers for glomerular endothelial cells. Some factors induced DKK2 when they were added at the late time point of the previous differentiation method (Patsch et al. Nat Cell Biol., 2015). Some factors also synergistically induced DKK2. DKK2 expression was more upregulated on the laminin 512-coating plate.

Academic Significance and Societal Importance of the Research Achievements

ヒト多能性幹細胞は様々な組織や細胞にも分化することが可能で、無限に増殖することができる。本研究成果をさらに発展させてヒト腎臓にある糸球体内皮細胞が作製可能となれば、糖尿病性腎症をはじめその他の腎症の病態解明や薬剤スクリーニングが飛躍的に進むことが期待される。また腎疾患に対する細胞移植療法の材料となる可能性も将来的には考えられる。

Report

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

    (13 results)

All 2021 2020 2019 Other

All Int'l Joint Research (1 results) Journal Article (12 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 12 results,  Open Access: 11 results)

  • [Int'l Joint Research] Beth Israel Deaconess Medical Center(米国)

    • Related Report
      2019 Research-status Report
  • [Journal Article] Treatment of Refractory Hypertension with Timely Angioplasty in Total Renal Artery Occlusion with Atrophic Kidney2021

    • Author(s)
      Sasaki Yuri、Mishima Eikan、Kikuchi Koichi、Toyohara Takafumi、Suzuki Takehiro、Ota Hideki、Seiji Kazumasa、Miyazaki Mariko、Harigae Hideo、Ito Sadayoshi、Takase Kei、Abe Takaaki
    • Journal Title

      Internal Medicine

      Volume: 60 Issue: 2 Pages: 287-292

    • DOI

      10.2169/internalmedicine.5290-20

    • NAID

      130007968948

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2021-01-15
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] L-type amino acid transporter 1 is associated with chemoresistance in breast cancer via the promotion of amino acid metabolism2021

    • Author(s)
      Sato Miku、Harada-Shoji Narumi、Toyohara Takafumi、Soga Tomoyoshi、Itoh Masatoshi、Miyashita Minoru、Tada Hiroshi、Amari Masakazu、Anzai Naohiko、Furumoto Shozo、Abe Takaaki、Suzuki Takashi、Ishida Takanori、Sasano Hironobu
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 589-589

    • DOI

      10.1038/s41598-020-80668-5

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Apparent Diffusion Coefficient in the Resolution of Renal Ischemia after Angioplasty on Diffusion-weighted Imaging: Renal Artery Stenosis Caused by Progressive Thrombosis in Residual Chronic Aortic Dissection2020

    • Author(s)
      Mishima Eikan、Ota Hideki、Suzuki Takehiro、Toyohara Takafumi、Seiji Kazumasa、Ito Sadayoshi、Saiki Yoshikatsu、Takase Kei、Abe Takaaki
    • Journal Title

      Internal Medicine

      Volume: 59 Issue: 9 Pages: 1173-1177

    • DOI

      10.2169/internalmedicine.3855-19

    • NAID

      130007839437

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2020-05-01
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mitochondrial dysfunction underlying sporadic inclusion body myositis is ameliorated by the mitochondrial homing drug MA-52020

    • Author(s)
      Oikawa Yoshitsugu、Izumi Rumiko、Koide Masashi、、、Aoki Masashi、Kure Shigeo、Abe Takaaki
    • Journal Title

      PLOS ONE

      Volume: 15 Issue: 12 Pages: e0231064-e0231064

    • DOI

      10.1371/journal.pone.0231064

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Germ-free conditions modulate host purine metabolism, exacerbating adenine-induced kidney damage.2020

    • Author(s)
      Mishima E, Ishijo M, Kawabe T, Kikuchi K, Akiyama Y, Toyohara T, Suzuki C, Asao A, Ishii N, Fukuda S, Abe T
    • Journal Title

      Toxins

      Volume: 12 Issue: 9 Pages: 547-547

    • DOI

      10.3390/toxins12090547

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Concurrent analogous organ damage in the brain, eyes, and kidneys in malignant hypertension: reversible encephalopathy, serous retinal detachment, and proteinuria2020

    • Author(s)
      Mishima E, Funayama Y, Suzuki T, Mishima F, Nitta F, Toyohara T, Kikuchi K, Kunikata H, Hashimoto J, Miyazaki M, Harigae H, Nakazawa T, Ito S, Abe T.
    • Journal Title

      Hypertension Research

      Volume: 44 Issue: 1 Pages: 88-97

    • DOI

      10.1038/s41440-020-0521-2

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Patient hiPSCs Identify Vascular Smooth Muscle Arylacetamide Deacetylase as Protective against Atherosclerosis2020

    • Author(s)
      Toyohara Takafumi、Roudnicky Filip、Florido Mary H.C.、Nakano Toshiaki、Yu Haojie、Katsuki Shunsuke、Lee Minjin、Meissner Torsten、Friesen Max、Davidow Lance S.、Ptaszek Leon、Abe Takaaki、Rubin Lee L.、Pereira Alexandre C.、Aikawa Masanori、Cowan Chad A.
    • Journal Title

      Cell Stem Cell

      Volume: 27 Issue: 1 Pages: 147-157.e7

    • DOI

      10.1016/j.stem.2020.04.018

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Kidney enlargement effect of angioplasty for nonatherosclerotic renovascular disease: reversibility of ischemic kidney2020

    • Author(s)
      Iwasaki Tomoyuki、Mishima Eikan、Suzuki Takehiro、Kikuchi Koichi、Toyohara Takafumi、Seiji Kazumasa、Takase Kei、Miyazaki Mariko、Harigae Hideo、Ito Sadayoshi、Abe Takaaki
    • Journal Title

      Hypertension Research

      Volume: 43 Issue: 11 Pages: 1214-1221

    • DOI

      10.1038/s41440-020-0473-6

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A nonhuman primate model of liver fibrosis towards cell therapy for liver cirrhosis.2020

    • Author(s)
      Yasuda K, Kotaka M, Toyohara T, Sueta SI, Katakai Y, Ageyama N, Uemoto S, Osafune K.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 20 Issue: 3 Pages: 30643-30644

    • DOI

      10.1016/j.bbrc.2020.03.148

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mitoregulin Controls β-Oxidation in Human and Mouse Adipocytes.2020

    • Author(s)
      Friesen M, Warren CR, Yu H, Toyohara T, Ding Q, Florido MHC, Sayre C, Pope BD, Goff LA, Rinn JL, Cowan CA.
    • Journal Title

      Stem Cell Reports

      Volume: 14 Issue: 4 Pages: 590-602

    • DOI

      10.1016/j.stemcr.2020.03.002

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] HPRT-related hyperuricemia with a novel p.V35M mutation in HPRT1 presenting familial juvenile gout.2020

    • Author(s)
      Mishima E, Mori T, Nakajima Y, Toyohara T, Kikuchi K, Oikawa Y, Matsuhashi T, Maeda Y, Suzuki T, Kudo M, Ito S, Sohara E, Uchida S, Abe T.
    • Journal Title

      CEN Case Rep

      Volume: pub Issue: 3 Pages: 210-214

    • DOI

      10.1007/s13730-020-00459-9

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] GPR146 Deficiency Protects against Hypercholesterolemia and Atherosclerosis2019

    • Author(s)
      Yu H、Rimbert A、Palmer AE.、Toyohara T、Xia Y、Xia F、Ferreira LMR.、Chen Z、Chen T、Loaiza N、Horwitz NB、Kacergis Michael C、Zhao L、Soukas AA.、Kuivenhoven JA、Kathiresan S、Cowan CA.
    • Journal Title

      Cell

      Volume: 179 Issue: 6 Pages: 1276-1288.e14

    • DOI

      10.1016/j.cell.2019.10.034

    • Related Report
      2019 Research-status Report
    • Peer Reviewed

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Published: 2019-09-03   Modified: 2022-01-27  

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