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Basic research on improvement of alveolar barrier function using adipose stem cells and novel cell therapy for ALI/ARDS

Research Project

Project/Area Number 21K08907
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55040:Respiratory surgery-related
Research InstitutionNagasaki University

Principal Investigator

Ishii Mitsutoshi  長崎大学, 医歯薬学総合研究科(医学系), 客員研究員 (60783066)

Co-Investigator(Kenkyū-buntansha) 宮崎 拓郎  長崎大学, 病院(医学系), 講師 (00584749)
土谷 智史  長崎大学, 医歯薬学総合研究科(医学系), 客員教授 (30437884)
永安 武  長崎大学, 医歯薬学総合研究科(医学系), 教授 (80284686)
佐原 寿史  鹿児島大学, 総合科学域総合研究学系, 准教授 (90452333)
Project Period (FY) 2021-04-01 – 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 2023: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords呼吸器再生 / 幹細胞治療 / 肺胞バリア機能 / 急性肺障害 / 慢性閉塞性肺疾患 / 脂肪由来間葉系幹細胞 / 急性呼吸窮迫症候群 / 間葉系幹細胞 / 急性肺障害/急性呼吸窮迫症候群
Outline of Research at the Start

間葉系幹細胞は骨髄や脂肪から採取される多分化能を持つ細胞であるが、肺胞上皮や内皮細胞を介したバリア機構を維持・修復するとされ、急性肺障害/急性呼吸窮迫症候群(ALI/ARDS)や損傷肺への治療効果が期待されている。一方、使用されている間葉系幹細胞は、殆どが骨髄由来のものである。本研究では、肺障害への細胞治療として脂肪由来間葉系幹細胞(ADSC)の骨髄由来間葉系幹細胞(BMSC)に対する優位性を多方面から証明し、臨床試験の基礎データとする。またブタを使用して肺に塞栓を形成しないか検証する。ADSCによる細胞治療は、COVID-19感染症や重症化肺炎後に起こるALI/ARDSへの治療選択肢となる。

Outline of Final Research Achievements

In this study, we investigated the therapeutic effect of mesenchymal stem cell (MSC) administration on chronic obstructive pulmonary disease (COPD), one of the basic respiratory diseases, and found that MSCs administered intravenously in a COPD mouse model grew in the lungs for a longer period than normal cultured cells and suppressed tissue damage through anti-inflammatory and immunosuppressive actions. The results showed that intravenous administration of MSCs in COPD model mice suppressed tissue damage through anti-inflammatory and immunosuppressive effects. Furthermore, MSCs showed highly efficient induction of differentiation into pulmonary capillary endothelial cells and myofibroblasts in the lung tissue, confirming their remarkable efficacy. Flow cytometric analysis of lung tissue after cell administration showed that macrophages in the cell administration group showed a change in polarity to M2 macrophages, suggesting their involvement in tissue repair.

Academic Significance and Societal Importance of the Research Achievements

ALI/ARDSへの細胞治療としてADSCによる細胞治療の有効性の基礎的データを得るための開始の研究として重要であり、特にADSCによる肺のバリア機能の強化を目的とした、未だ行われていない研究である。今後、ブタ肺虚血再灌流モデルでALI/ARDSを誘発し、ADSC静脈投与の有用性、安全性を証明することによって、ALI/ARDSの新たな治療選択肢としてADSCの細胞治療を確立できる。

Report

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

    (3 results)

All 2024 2022 2021

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 2 results)

  • [Journal Article] Designer umbilical cord-stem cells induce alveolar wall regeneration in pulmonary disease models2024

    • Author(s)
      Iwatake Mayumi、Nagamura-Inoue Tokiko、Doi Ryoichiro、Tanoue Yukinori、Ishii Mitsutoshi、Yukawa Hiroshi、Matsumoto Keitaro、Tomoshige Koichi、Nagayasu Takeshi、Tsuchiya Tomoshi
    • Journal Title

      Frontiers in Immunology

      Volume: 15 Pages: 1-13

    • DOI

      10.3389/fimmu.2024.1384718

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Donor and Recipient Adipose-Derived Mesenchymal Stem Cell Therapy for Rat Lung Transplantation2022

    • Author(s)
      Shimoyama Koichiro、Tsuchiya Tomoshi、Watanabe Hironosuke、Ergalad Abdelmotagaly、Iwatake Mayumi、Miyazaki Takuro、Hashimoto Yasumasa、Hsu Yu-I.、Hatachi Go、Matsumoto Keitaro、Ishii Mitsutoshi、Mizoguchi Satoshi、Doi Ryoichiro、Tomoshige Koichi、Yamaoka Tetsuji、Nagayasu Takeshi
    • Journal Title

      Transplantation Proceedings

      Volume: 54 Issue: 7 Pages: 1998-2007

    • DOI

      10.1016/j.transproceed.2022.05.038

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Increased In Vitro Intercellular Barrier Function of Lung Epithelial Cells Using Adipose-Derived Mesenchymal Stem/Stromal Cells2021

    • Author(s)
      Ishii Mitsutoshi、Tsuchiya Tomoshi、Doi Ryoichiro、Morofuji Yoichi、Fujimoto Takashi、Muto Hideki、Suematsu Takashi、Mori Ryoichi、Matsumoto Keitaro、Miyazaki Takuro、Tomoshige Koichi、Watanabe Hironosuke、Iwatake Mayumi、Nagayasu Takeshi
    • Journal Title

      Pharmaceutics

      Volume: 13 Issue: 8 Pages: 1264-1264

    • DOI

      10.3390/pharmaceutics13081264

    • NAID

      120007172252

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access

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

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