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Establishment of three-dimensional laminated lymphatic network autografts based on adipose tissue-derived stem cells (ASCs)

Research Project

Project/Area Number 17K08506
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General anatomy (including histology/embryology)
Research InstitutionHirosaki University

Principal Investigator

Asano Yoshiya  弘前大学, 医学研究科, 講師 (50359494)

Co-Investigator(Kenkyū-buntansha) 下田 浩  弘前大学, 医学研究科, 教授 (20274748)
Project Period (FY) 2017-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords人工脈管組織 / 間葉系幹細胞 / リンパ管 / 血管 / リンパ浮腫 / 三次元人工脈管組織 / 脂肪組織由来間葉系幹細胞 / 三次元培養 / 三次元人工リンパ管網組織 / 脂肪組織由来幹細胞 / 再生医療
Outline of Final Research Achievements

Artificial three-dimensional vascular network tissues based on human adipose tissue-derived mesenchymal stem cells (hASCs) were constructed due to the aim of regenerative medicine for secondary lymphedema. Compared to the previous fibroblast-based cases, the promotion of vascular and lymphatic network formation was observed, and the three-dimensional hASC-based tissue was found to be more effective than the conventional fibroblast-based case in the formation of vascular network. The results suggested that the enhancement of expression of angiogenesis-related factors by hASCs was involved. Transplantation of vascular network tissue resulted in good engraftment with pericyte or smooth muscle-like differentiation of hASCs. On the other hand, transplantation of lymphatic network tissue showed regression of vascular vessels, but the results in the mouse model of lymphatic flow regeneration suggested anastomosis between deep and superficial lymphatic vessels and new channel formation.

Academic Significance and Societal Importance of the Research Achievements

本研究により、自己由来細胞として低侵襲で採取可能なhASCを用いた人工脈管網組織が移植可能であり、血管網組織については機能的な微小血管床が形成されることを示した。また、リンパ管網組織は脈管の生着は限定的だが、欠損したリンパ管網の吻合に寄与することが示唆され、従来の手法に比べてより有効な治療法を提供しうると考えられる。また、細胞凍結技術を融合した迅速な人工脈管組織構築技術を開発した。これらは、脈管形成過程の基礎研究ならびに脈管組織の再生医療研究に寄与しうる成果である。

Report

(6 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (18 results)

All 2021 2020 2019 2018 2017

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 2 results) Presentation (10 results)

  • [Journal Article] Construction of transplantable artificial vascular tissue based on adipose tissue-derived mesenchymal stromal cells by a cell coating and cryopreservation technique2021

    • Author(s)
      Asano Y, Okano D, Matsusaki M, Watabe T, Yoshimatsu Y, Akashi M, Shimoda H
    • Journal Title

      Scientific reports

      Volume: 11 Issue: 1 Pages: 17989-17989

    • DOI

      10.1038/s41598-021-97547-2

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Cell Line-Dependent Diversity in Initial Morphological Dynamics of Pancreatic Cancer Cell Peritoneal Metastasis Visualized by an Artificial Human Peritoneal Model2021

    • Author(s)
      Odagiri T, Asano Y, Kagiya T, Matsusaki M, Akashi M, Shimoda H, Hakamada K.
    • Journal Title

      journal of surgical research

      Volume: 261 Pages: 351-360

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] In Vitro Evaluation System of Pharmacokinetics and Irradiation Effect in Boron Neutron Capture Therapy (BNCT) Using Three-Dimensional Artificial Human Tumor Tissue Model2019

    • Author(s)
      Shintaro Ishiyama, Yoshiya Asano, Minoru Suzuki, Mitsuru Akashi, Hiroshi Shimoda
    • Journal Title

      Journal of Cancer Therapy

      Volume: 10 Issue: 10 Pages: 835-845

    • DOI

      10.4236/jct.2019.1010071

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Morphological analysis of peritoneal dissemination of ovarian cancer based on levels of carbonyl reductase 1 expression2019

    • Author(s)
      Fumie Oyama, Yoshiya Asano, Hiroshi Shimoda, Kayo Horie, Jun Watanabe, Yoshihito Yokoyama
    • Journal Title

      European Journal of Gynaecological Oncology

      Volume: in press

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Inhibitory effect of carbonyl reductase 1 against peritoneal progression of ovarian cancer: Evaluation by ex-vivo 3D-human peritoneal model2019

    • Author(s)
      Hiroe Oikiri, Yoshiya Asano, Michiya Matsusaki, Mitsuru Akashi, Hiroshi Shimoda, Yoshihito Yokoyama
    • Journal Title

      Molecular Biology Reports

      Volume: in press

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] In vitro 3D blood/lymph-vascularized human stromal tissues for preclinical assays of cancer metastasis2018

    • Author(s)
      Nishiguchi Akihiro、Matsusaki Michiya、Kano Mitsunobu R.、Nishihara Hiroshi、Okano Daisuke、Asano Yoshiya、Shimoda Hiroshi、Kishimoto Satoko、Iwai Soichi、Akashi Mitsuru
    • Journal Title

      Biomaterials

      Volume: 179 Pages: 144-155

    • DOI

      10.1016/j.biomaterials.2018.06.019

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Transplantation of artificial human lymphatic vascular tissues fabricated using a cell-accumulation technique and their engraftment in mouse tissue with vascular remodelling2018

    • Author(s)
      Asano Y, Shimoda H, Matsusaki M, Akashi M
    • Journal Title

      J Tissue Eng Regen Med

      Volume: 12

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Construction of artificial human peritoneal tissue by cell-accumulation technique and its application for visualizing morphological dynamics of cancer peritoneal metastasis2017

    • Author(s)
      Asano Y, Odagiri T, Oikiri H, Matsusaki M, Akashi M, Shimoda H
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 949 Pages: 213-219

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] 間葉系幹細胞を基盤とした三次元人工リンパ管ネットワーク組織の移植とリンパ流路形成2021

    • Author(s)
      浅野義哉、岡野大輔、齊藤絵里奈、明石満、下田浩
    • Organizer
      第67回 東北・北海道連合支部学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 間葉系幹細胞を基盤とした三次元人工神経組織の構築2021

    • Author(s)
      浅野義哉、齊藤絵里奈、岡野大輔、松崎典弥、明石満、下田浩
    • Organizer
      第158回弘前医学会例会
    • Related Report
      2020 Research-status Report
  • [Presentation] 三次元ヒト人工腹膜組織を用いた癌腹膜播種動態および治療に 関する研究2020

    • Author(s)
      浅野義哉、小田切理、追切裕江、小山文望恵、松崎典弥、横山良仁、袴田健一、明石満、下田浩
    • Organizer
      日本解剖学会第66回東北・北海道連合支部学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] 間葉系幹細胞と神経芽腫細胞株SH-SY5Yを用いた人工ヒト脈管神経網組織の構築2020

    • Author(s)
      浅野義哉、岡野大輔、齊藤絵里奈、松崎典弥、明石満、下田浩
    • Organizer
      第125回 日本解剖学会総会・全国学術集会 (誌上開催)
    • Related Report
      2019 Research-status Report
  • [Presentation] ヒト脂肪組織由来間葉系幹細胞を基盤とした三次元組織の構築と応用2019

    • Author(s)
      浅野義哉、岡野大輔、齊藤絵里奈、明石満、下田浩
    • Organizer
      日本解剖学会第65回東北北海道連合支部学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 三次元人工ヒト脈管ネットワーク形成における脂肪組織由来間葉系幹細胞(ASC)の動態と効果2019

    • Author(s)
      浅野義哉、岡野大輔、松﨑典弥、明石満、下田浩
    • Organizer
      第18回日本再生医療学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 脂肪組織由来間葉系幹細胞を主体とした人工ヒト脈管網組織の構築と移植2019

    • Author(s)
      浅野義哉、岡野大輔、畠中大維、松崎典弥、明石満、下田浩
    • Organizer
      第124回日本解剖学会総会・全国学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 三次元人工ヒト血管およびリンパ管ネットワーク構築における脂肪組織由来間葉系幹細胞(ASC)の効果2018

    • Author(s)
      浅野義哉、野口光司、岡野大輔、松崎典弥、明石満、下田 浩
    • Organizer
      第42回日本リンパ学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] ヒト三次元人工組織を用いた、脂肪組織由来間葉系幹細胞(ASC)による血管およびリンパ管ネットワーク構築調節の解析2018

    • Author(s)
      浅野義哉、野口光司、岡野大輔、松崎典弥、明石満、下田浩
    • Organizer
      第123回日本解剖学会総会・全国学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 人工三次元ヒトリンパ管網組織の移植によるリンパ流路再生誘導2017

    • Author(s)
      浅野義哉 松崎典弥 明石満 下田浩
    • Organizer
      第41回日本リンパ学会総会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2024-12-25  

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