• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Elucidation of the regulatory mechanism of pluripotency of umbilical cord-derived Muse cells and development of novel therapies for placental insufficiency

Research Project

Project/Area Number 20K07218
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 48010:Anatomy-related
Research InstitutionTohoku University

Principal Investigator

Kushida Yoshihiro  東北大学, 医学系研究科, 助教 (10707003)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsMuse細胞 / 胎児付属物 / 臍帯 / 多能性幹細胞
Outline of Research at the Start

Muse細胞は生体組織に存在する腫瘍性を持たない多能性幹細胞である。この細胞は多能性幹細胞マーカーであるSSEA-3を指標に採取でき、直接血管内や局所に移植するだけで、傷害組織へ遊走・集積し、組織に応じた細胞に自発的に分化して組織修復を行う。そのため、安全性と簡便性を併せ持つMuse細胞は細胞移植治療に適した細胞であると考えられている。本研究では、未解明である臍帯由来Muse細胞の多能性制御機構および胎盤機能不全に対する治療効果を検証することで、再生医療におけるMuse細胞の利用可能性の幅を広げることを目的とする。

Outline of Final Research Achievements

To elucidate the characteristics and pluripotency regulatory mechanisms of umbilical cord-derived Muse cells as a novel cell source of Muse cells, which are non-tumorigenic pluripotent stem cells, we performed gene expression and DNA methylation analyses of umbilical cord-, bone marrow-, adipose- and skin-derived Muse cells. Comparison with human embryo data revealed that umbilical cord-derived Muse cells exhibit properties similar to those of post-implantation blastocysts. Furthermore, we identified the factor specifically expressed in umbilical cord-derived Muse cells that regulates pluripotency. It was found that umbilical cord-derived Muse cells have the ability to differentiate into not only triploblastic cells but also trophoblasts, germline, and hematopoietic cells. These results established the foundation for applications in the perinatal care and reproductive medicine.

Academic Significance and Societal Importance of the Research Achievements

生体組織に存在する腫瘍性を持たない多能性幹細胞であるMuse細胞は直接血管内や局所に投与するだけで、傷害組織へ遊走・集積し、組織に応じた細胞に自発的に分化して組織修復を行う。そのため、安全性と簡便性を併せ持つMuse細胞は細胞移植治療に適した細胞であると考えられている。本研究を通じて新規細胞ソースとして臍帯由来Muse細胞の多能性制御機構の解明と胚体外組織や生殖細胞系列への分化能を持つことが明らかになった。このことからMuse細胞は治験が行われている心筋梗塞や脳梗塞などの疾患に加え、周産期領域や生殖医学への応用が期待される。

Report

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

    (16 results)

All 2022 2021 2020

All Journal Article (15 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 15 results,  Open Access: 15 results) Presentation (1 results)

  • [Journal Article] Intravenous administration of human Muse cells recovers blood flow in a mouse model of hindlimb ischemia2022

    • Author(s)
      Hori Yusuke、Kitani Tomoya、Yanishi Kenji、Suga Takaomi、Kogure Masaya、Kusaba Tetsuro、Kushida Yoshihiro、Dezawa Mari、Matoba Satoaki
    • Journal Title

      Frontiers in Cardiovascular Medicine

      Volume: 9 Pages: 981088-981088

    • DOI

      10.3389/fcvm.2022.981088

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Single-cell RNA sequencing reveals different signatures of mesenchymal stromal cell pluripotent-like and multipotent populations2022

    • Author(s)
      Oguma Yo、Kuroda Yasumasa、Wakao Shohei、Kushida Yoshihiro、Dezawa Mari
    • Journal Title

      iScience

      Volume: 25 Issue: 11 Pages: 105395-105395

    • DOI

      10.1016/j.isci.2022.105395

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Naive pluripotent-like characteristics of non-tumorigenic Muse cells isolated from human amniotic membrane2022

    • Author(s)
      Ogawa Eiji、Oguma Yo、Kushida Yoshihiro、Wakao Shohei、Okawa Kana、Dezawa Mari
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 17222-17222

    • DOI

      10.1038/s41598-022-22282-1

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Phagocytosing differentiated cell-fragments is a novel mechanism for controlling somatic stem cell differentiation within a short time frame2022

    • Author(s)
      Wakao S, Oguma Y, Kushida Y, Kuroda Y, Tatsumi K, Dezawa M
    • Journal Title

      Cellular and Molecular Life Sciences

      Volume: 79 Issue: 11 Pages: 542-542

    • DOI

      10.1007/s00018-022-04555-0

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibition of Gap Junctional Intercellular Communication Upregulates Pluripotency Gene Expression in Endogenous Pluripotent Muse Cells2022

    • Author(s)
      Hatabi Khaled、Hirohara Yukari、Kushida Yoshihiro、Kuroda Yasumasa、Wakao Shohei、Trosko James、Dezawa Mari
    • Journal Title

      Cells

      Volume: 11 Issue: 17 Pages: 2701-2701

    • DOI

      10.3390/cells11172701

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Isolation and characterization of bone marrow-derived mesenchymal stem cells in Xenopus laevis.2021

    • Author(s)
      Otsuka-Yamaguchi R, Kitada M, Kuroda Y, Kushida Y, Wakao S, Dezawa M.
    • Journal Title

      Stem Cell Res

      Volume: 53 Pages: 102341-102341

    • DOI

      10.1016/j.scr.2021.102341

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Non-Tumorigenic Pluripotent Reparative Muse Cells Provide a New Therapeutic Approach for Neurologic Diseases2021

    • Author(s)
      Yamashita Toru、Kushida Yoshihiro、Abe Koji、Dezawa Mari
    • Journal Title

      Cells

      Volume: 10 Issue: 4 Pages: 961-961

    • DOI

      10.3390/cells10040961

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Protection of liver sinusoids by intravenous administration of human Muse cells in a rat extra‐small partial liver transplantation model2021

    • Author(s)
      Shono Yoshihiro、Kushida Yoshihiro、Wakao Shohei、Kuroda Yasumasa、Unno Michiaki、Kamei Takashi、Miyagi Shigehito、Dezawa Mari
    • Journal Title

      American Journal of Transplantation

      Volume: Online ahead of print Issue: 6 Pages: 2025-2039

    • DOI

      10.1111/ajt.16461

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Intravenous Injection of Muse Cells as a Potential Therapeutic Approach for Epidermolysis Bullosa2021

    • Author(s)
      Fujita Yasuyuki、Komatsu Miho、Lee San Eun、Kushida Yoshihiro、Nakayama-Nishimura Chihiro、Matsumura Wakana、Takashima Shota、Shinkuma Satoru、Nomura Toshifumi、Masutomi Naoya、Kawamura Makoto、Dezawa Mari、Shimizu Hiroshi
    • Journal Title

      Journal of Investigative Dermatology

      Volume: 141 Issue: 1 Pages: 198-202.e6

    • DOI

      10.1016/j.jid.2020.05.092

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Comparison of separation methods for tissue-derived extracellular vesicles in the liver, heart, and skeletal muscle2021

    • Author(s)
      Matejovic A, Wakao S, Kitada M, Kushida Y, Dezawa M
    • Journal Title

      FEBS Open Bio

      Volume: 11 Issue: 2 Pages: 482-493

    • DOI

      10.1002/2211-5463.13075

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Intravenously Transplanted Human Multilineage-Differentiating Stress-Enduring Cells Afford Brain Repair in a Mouse Lacunar Stroke Model.2020

    • Author(s)
      Abe T, Aburakawa D, Niizuma K, Iwabuchi N, Kajitani T, Wakao S, Kushida Y, Dezawa M, Borlongan CV, Tominaga T.
    • Journal Title

      Stroke.

      Volume: 51(2) Issue: 2 Pages: 601-611

    • DOI

      10.1161/strokeaha.119.026589

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A Novel Type of Stem Cells Double-Positive for SSEA-3 and CD45 in Human Peripheral Blood2020

    • Author(s)
      Sato Tetsuya、Wakao Shohei、Kushida Yoshihiro、Tatsumi Kazuki、Kitada Masaaki、Abe Takatsugu、Niizuma Kuniyasu、Tominaga Teiji、Kushimoto Shigeki、Dezawa Mari
    • Journal Title

      Cell Transplantation

      Volume: Online ahead of print Pages: 096368972092357-096368972092357

    • DOI

      10.1177/0963689720923574

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Intravenously delivered multilineage-differentiating stress enduring cells dampen excessive glutamate metabolism and microglial activation in experimental perinatal hypoxic ischemic encephalopathy2020

    • Author(s)
      Suzuki Toshihiko、Sato Yoshiaki、Kushida Yoshihiro、Tsuji Masahiro、Wakao Shohei、Ueda Kazuto、Imai Kenji、Iitani Yukako、Shimizu Shinobu、Hida Hideki、Temma Takashi、Saito Shigeyoshi、Iida Hidehiro、Mizuno Masaaki、Takahashi Yoshiyuki、Dezawa Mari、Borlongan Cesar V、Hayakawa Masahiro
    • Journal Title

      Journal of Cerebral Blood Flow & Metabolism

      Volume: 0 Issue: 7 Pages: 1-14

    • DOI

      10.1177/0271678x20972656

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Therapeutic benefit of Muse cells in a mouse model of amyotrophic lateral sclerosis2020

    • Author(s)
      Yamashita Toru、Kushida Yoshihiro、Wakao Shohei、Tadokoro Koh、Nomura Emi、Omote Yoshio、Takemoto Mami、Hishikawa Nozomi、Ohta Yasuyuki、Dezawa Mari、Abe Koji
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 17102-17102

    • DOI

      10.1038/s41598-020-74216-4

    • NAID

      120006900786

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The evaluation of the safety and efficacy of intravenously administered allogeneic multilineage-differentiating stress-enduring cells in a swine hepatectomy model2020

    • Author(s)
      Iseki Masahiro、Mizuma Masamichi、Wakao Shohei、Kushida Yoshihiro、Kudo Katsuyoshi、Fukase Masahiko、Ishida Masaharu、Ono Tomoyuki、Shimura Mitsuhiro、Ise Ichiro、Suzuki Yukie、Sueta Teruko、Asada Ryuta、Shimizu Shinobu、Ueno Yoshiyuki、Dezawa Mari、Unno Michiaki
    • Journal Title

      Surgery Today

      Volume: 51 Issue: 4 Pages: 634-650

    • DOI

      10.1007/s00595-020-02117-0

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Kinetic analysis and therapeutic effect of Muse cells using bioluminescence imaging2022

    • Author(s)
      Yoshihiro Kushida, Mari Dezawa
    • Organizer
      日本顕微鏡学会 第78回学術講演会
    • Related Report
      2022 Annual Research Report

URL: 

Published: 2020-04-28   Modified: 2024-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi