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Elucidation of the pathogenesis of severe lymphedema focusing on pericytes in lymphatic vessel walls

Research Project

Project/Area Number 21K16924
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 56070:Plastic and reconstructive surgery-related
Research InstitutionShimane University

Principal Investigator

Hayashida Kenji  島根大学, 学術研究院医学・看護学系, 准教授 (50599933)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2023: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords創傷治癒 / リンパ浮腫 / ペリサイト / モデルマウス / 脂肪由来幹細胞 / 再生医療 / 幹細胞 / リンパ管
Outline of Research at the Start

線維化の著しい重度リンパ浮腫患者への根治的治療法は確立されていない。近年、皮膚・皮下組織の線維化には、筋線維芽細胞に分化するペリサイトの関与が推察されており、その線維化機序に関する知見が集積してきた。
本研究は、リンパ管壁に局在するペリサイトが、リンパ浮腫状態で生じる活性化・分化の機序を、脂肪由来幹細胞を使ったサイトカイン産生プロファイルの観点から徹底解明する。この研究によって、ペリサイトが筋線維芽細胞へと分化する際のバランス制御をターゲットとした、重度リンパ浮腫に対する新たな選択的予防法・治療法の研究基盤が確立できる。

Outline of Final Research Achievements

In lymphedema model mice, macrophages and bone marrow-derived cells were also confirmed to accumulate in lymphedema. Furthermore, we reported that chronic edema occurring on the face, mainly around the eyelids, may also be a disease related to lymphedema. Observations of pericytes during the study period suggested that they were related to lymphedema, but differentiation into myofibroblasts and other cells was not clear, and creation of a pericyte-free model mouse was unsuccessful. Therefore, further information gathering, including detailed consideration of the creation of a pericyte-free model mouse, and exchange of opinions with experts studying cerebrovascular pericytes and retinal pericytes are considered necessary in the future.

Academic Significance and Societal Importance of the Research Achievements

癌治療後にリンパ浮腫を発症する患者は、本邦を含む全世界で増加傾向にある。しかしながら、その発症機序は未解明な部分が多く、線維化の著しい重度リンパ浮腫患者への根治的治療法は確立されていない。近年、皮膚・皮下組織の線維化には、筋線維芽細胞に分化するペリサイトの関与が推察されている。本研究ではリンパ管壁に局在するペリサイトが、リンパ浮腫状態で生じる活性化・分化の機序を、脂肪由来幹細胞を使ったサイトカイン産生プロファイルの観点から徹底解明した。ペリサイトが筋線維芽細胞へと分化する際のバランス制御をターゲットとした、重度リンパ浮腫に対する新たな選択的予防法・治療法の研究基盤の一部を確立した。

Report

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

    (14 results)

All 2023 2022 2021

All Journal Article (10 results) (of which Peer Reviewed: 10 results,  Open Access: 9 results) Presentation (4 results) (of which Int'l Joint Research: 3 results,  Invited: 4 results)

  • [Journal Article] Scanning Electron Microscopy Analysis of Lymphatic Regeneration in a Secondary Lymphedema Mouse Model: A Preliminary Study2023

    • Author(s)
      Hayashida Kenji、Ogino Ryohei、Suda Shota、Yamakawa Sho
    • Journal Title

      Lymphatics

      Volume: 1 Issue: 3 Pages: 237-243

    • DOI

      10.3390/lymphatics1030014

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Scrotal Reconstruction Using a Free Ulnar Forearm Flap: A Case Report2022

    • Author(s)
      Yamakawa Sho、Hayashida Kenji
    • Journal Title

      Journal of Plastic and Reconstructive Surgery

      Volume: 1 Issue: 1 Pages: 26-30

    • DOI

      10.53045/jprs.2021-0011

    • NAID

      130008145188

    • ISSN
      2436-259X
    • Year and Date
      2022-01-27
    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role and Function of Mesenchymal Stem Cells on Fibroblast in Cutaneous Wound Healing2022

    • Author(s)
      Tanaka Kotaro、Ogino Ryohei、Yamakawa Sho、Suda Shota、Hayashida Kenji
    • Journal Title

      Biomedicines

      Volume: 10 Issue: 6 Pages: 1391-1391

    • DOI

      10.3390/biomedicines10061391

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Emerging Anti-Inflammatory Pharmacotherapy and Cell-Based Therapy for Lymphedema2022

    • Author(s)
      Ogino Ryohei、Yokooji Tomoharu、Hayashida Maiko、Suda Shota、Yamakawa Sho、Hayashida Kenji
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 23 Issue: 14 Pages: 7614-7614

    • DOI

      10.3390/ijms23147614

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Surgical Management for Foul-Smelling Wounds2022

    • Author(s)
      Hayashida Kenji、Suda Shota、Yamakawa Sho
    • Journal Title

      International Journal of Surgical Wound Care

      Volume: 3 Issue: 4 Pages: 149-151

    • DOI

      10.36748/ijswc.3.4_149

    • ISSN
      2435-2128
    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Safety and efficacy of secondary mandibular reconstruction using a free osteo-cutaneous fibula flap after segmental mandibular resection: a retrospective case?control study2021

    • Author(s)
      Yamakawa Sho、Hayashida Kenji
    • Journal Title

      BMC Surgery

      Volume: 21 Issue: 1 Pages: 189-189

    • DOI

      10.1186/s12893-021-01194-3

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Postoperative oral dysfunction following oral cancer resection and reconstruction: A preliminary cross-sectional study2021

    • Author(s)
      Matsuda Yuhei、Okui Tatsuo、Karino Masaaki、Aoi Noriaki、Okuma Satoe、Hayashida Kenji、Sakamoto Tatsunori、Kanno Takahiro
    • Journal Title

      Oral Oncology

      Volume: 121 Pages: 105468-105468

    • DOI

      10.1016/j.oraloncology.2021.105468

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Development of a Subjective Symptom Rating Scale for Postoperative Oral Dysfunction in Patients with Oral Cancer: Reliability and Validity of the Postoperative Oral Dysfunction Scale-102021

    • Author(s)
      Matsuda Yuhei、Kumakura Isami、Okui Tatsuo、Karino Masaaki、Aoi Noriaki、Okuma Satoe、Takeda Mayu、Hayashida Kenji、Sakamoto Tatsunori、Kanno Takahiro
    • Journal Title

      Diagnostics

      Volume: 11 Issue: 11 Pages: 2061-2061

    • DOI

      10.3390/diagnostics11112061

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fournier's gangrene with subcutaneous emphysema of the thigh caused by air inflow associated with a rectovaginal fistula: a case report of pseudo-gas gangrene.2021

    • Author(s)
      Yamakawa S, Fujioka M, Fukui K, Matsuo H, Noguchi M, Kugiyama T, Sugimi S, Fukuda H, Hayashida K
    • Journal Title

      WOUNDS

      Volume: 33 Pages: 10-13

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Topical odour management in burn patients2021

    • Author(s)
      Hayashida Kenji、Yamakawa Sho
    • Journal Title

      Burns & Trauma

      Volume: 9

    • DOI

      10.1093/burnst/tkab025

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 重度リンパ浮腫の “point of no return” を改善できるか2023

    • Author(s)
      林田健志
    • Organizer
      第53回日本創傷治癒学会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Revolutionizing Reconstruction: Synergizing Regenerative Medicine and Vascularized Lymph Node Transfer for Optimal Patient Outcomes2023

    • Author(s)
      Kenji Hayashida
    • Organizer
      12th Congress of the World Society for Reconstructive Microsurgery
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Advances in growth factors for wound healing.2021

    • Author(s)
      Hayashida K
    • Organizer
      23rd Annual Conference of Indian Society of Wound Management
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Topical odor management of infected wounds.2021

    • Author(s)
      Hayashida K
    • Organizer
      23rd Annual Conference of Indian Society of Wound Management
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research / Invited

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Published: 2021-04-28   Modified: 2025-01-30  

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