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Analysis of metabolic pathways in adipose tissue-derived mesenchymal stem cells-hematopoietic stem cells: focus on anti-aging effects

Research Project

Project/Area Number 20K08721
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 54010:Hematology and medical oncology-related
Research InstitutionAichi Medical University

Principal Investigator

Nakayama Takayuki  愛知医科大学, 医学部, 教授 (00456659)

Co-Investigator(Kenkyū-buntansha) 都築 忍  愛知医科大学, 医学部, 教授 (00342965)
Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords血液凝固 / 脂肪組織由来間葉系幹細胞 / 造血支持能力 / Ebf3 / shRNA / ノックダウン / 脂肪細胞分化 / 骨髄造血微小環境 / 間葉系幹細胞 / メタボローム解析
Outline of Research at the Start

我々は、脂肪組織由来間葉系幹細胞(ADSC)がもつ高い造血支持能力を明らかとした。しかしその機序は未解明である。その後の研究により間葉系幹細胞における代謝関連遺伝子の発現と造血支持能力が相関することやADSCのもつ抗加齢作用が判明した。そこで我々は、ADSCは代謝を通じたHSC抗加齢作用により高い造血支持能力を有していると推定した。以上を検証するためADSCとHSCの共培養後にHSCのトランスクリプトーム、メタボロームやDNA metylationの解析を行う。候補が絞り込めたらその経路を同定する。またマウスへのADSC投与によりHSC数やDNAダメージに変化があるか確認する。

Outline of Final Research Achievements

We found that ADSCs have better hematopoietic support than BMSCs, but the mechanism is unknown; it has been reported that the transcription factor Ebf3 is abundantly expressed in BMSCs and maintains hematopoietic support by preventing differentiation into osteoblasts. We observed that BMSCs differentiated into adipocytes and osteoblasts, while ADSCs hardly differentiated into osteoblasts, and ADSCs abundantly expressed Ebf3. Since ADSCs have stronger blood coagulation activity than BMSCs (which promotes tissue repair), we have changed the course of our research and are now analyzing ADSCs for their effects on blood coagulation.

Academic Significance and Societal Importance of the Research Achievements

我々の観察では、BMSCは、脂肪細胞と骨芽細胞に分化したが、ADSCにおいては脂肪細胞によく分化したが骨芽細胞にほとんど分化しなかった。そのためADSCにおいては、Ebf3が強力に骨芽細胞分化を抑制することにより造血支持機能を残存していると予想した。そこでEbf3をノックダウンして機能の解析を試みたが、うまく機能しなかった。ADSCは、BMSCよりも強い血液凝固作用(組織修復を促進する)を有していたため方針転換を行いADSCのその作用について解析を行なっている。骨髄における造血と血液凝固の相関は、ほとんど報告されておらず、新たな研究テーマとなりうる可能性がある。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (5 results)

All 2023 2021

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 4 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Serum Produced from Expired Fresh Frozen Plasma and Cryosupernatant Supports the Proliferation of Human Cells: Cost-Effective Alternatives to Fetal Bovine Serum2023

    • Author(s)
      Kazuki Ishiyama, Mika Ogawa, Hidefumi Kato, Kyosuke Takeshita, Ryuzo Ueda, Takayuki Nakayama
    • Journal Title

      J Blood Disord Transfus

      Volume: 14 Pages: 1-6

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Point‐of‐care nerve conduction device predicts the severity of diabetic polyneuropathy: A quantitative, but easy‐to‐use, prediction model2021

    • Author(s)
      Kamiya Hideki、Shibata Yuka、Himeno Tatsuhito、Tani Hiroya、Nakayama Takayuki、Murotani Kenta、Hirai Nobuhiro、Kawai Miyuka、Asada‐Yamada Yuriko、Asano‐Hayami Emi、Nakai‐Shimoda Hiromi、Yamada Yuichiro、Ishikawa Takahiro、Morishita Yoshiaki、Kondo Masaki、Tsunekawa Shin、Kato Yoshiro、Baba Masayuki、Nakamura Jiro
    • Journal Title

      Journal of Diabetes Investigation

      Volume: 12 Issue: 4 Pages: 583-591

    • DOI

      10.1111/jdi.13386

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pretreatment Immature Platelet Fraction as a Surrogate of Reticulated Platelets Predicts the Response to Corticosteroids in Adults with Immune Thrombocytopenia2021

    • Author(s)
      Takami Akiyoshi、Mizuno Shohei、Nakamura Ayano、Kanasugi Jo、Yamamoto Hidesuke、Vu?Quang Lam、Nakagami Yuya、Nakano Yuta、Yamada Saki、Matsumura Saori、Takasugi Souichi、Uchino Kaori、Horio Tomohiro、Murakami Satsuki、Oohigashi Yuka、Nakayama Takayuki、Tani Hiroya、Enomoto Megumi、Hanamura Ichiro
    • Journal Title

      Acta Haematologica

      Volume: 144 Issue: 3 Pages: 345-349

    • DOI

      10.1159/000510460

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Alterations of retinal thickness measured by optical coherence tomography correlate with neurophysiological measures in diabetic polyneuropathy2021

    • Author(s)
      Yamada Y.、Himeno T.、Tsuboi K.、Shibata Y.、Kawai M.、Asada‐Yamada Y.、Hayashi Y.、Asano‐Hayami E.、Hayami T.、Ishida Y.、Ejima Y.、Motegi M.、Asano S.、Kato M.、Nagao E.、Nakai‐Shimoda H.、Ishikawa T.、Morishita Y.i、Kondo M.、Tsunekawa S.、Kato Y.、Nakayama T.、Kamei M.、Nakamura J.、Kamiya H.
    • Journal Title

      Journal of Diabetes Investigation

      Volume: 12 Issue: 8 Pages: 1430-1441

    • DOI

      10.1111/jdi.13476

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Patent(Industrial Property Rights)] 間葉系幹細胞を含有する局所止血剤2023

    • Inventor(s)
      中山享之、小川実加
    • Industrial Property Rights Holder
      中山享之、小川実加
    • Industrial Property Rights Type
      特許
    • Filing Date
      2023
    • Related Report
      2023 Annual Research Report

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Published: 2020-04-28   Modified: 2025-01-30  

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