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Development of Osteoid organoid technology for bone regeneration therapy

Research Project

Project/Area Number 21H03116
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 57030:Conservative dentistry-related
Research InstitutionTohoku University

Principal Investigator

Saito Masahiro  東北大学, 歯学研究科, 教授 (40215562)

Co-Investigator(Kenkyū-buntansha) 稲垣 雅彦  国立研究開発法人産業技術総合研究所, 材料・化学領域, 主任研究員 (10356488)
八幡 祥生  東北大学, 歯学研究科, 准教授 (30549944)
山田 聡  東北大学, 歯学研究科, 教授 (40359849)
田中 志典  東北大学, 大学病院, 講師 (60637958)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2023: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2022: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2021: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
Keywords再生医療 / 骨芽細胞 / 組織工学 / 骨生物学 / 移植治療 / 造骨 / 足場 / 水平性骨欠損 / 歯科医療 / 歯周組織 / 足場材料 / オルガノイド / 品質管理 / 骨 / 細胞移植 / 足場材
Outline of Research at the Start

近年、急速に進歩を遂げた幹細胞・発生生物学の知見を駆使することで、様々な疾患に対する再生医療の実用化が可能になった。本課題では骨形成の原基である類骨を形成させ、移植に用いることで造骨促進効果を得られる3次元オルガノイド培養法を用いた再生医療技術を考案した。期間内に研究代表者の開発したヒト歯槽骨から確立したヒト未分化骨芽細胞様細胞(HAOB)をin vitroで細胞凝集体にしオルガノイドを作製し、類骨に分化誘導した状態で移植に用いて早期に水平性骨欠損部位に垂直方向への造骨を可能にする「革新的類骨オルガノイド再生療法の基盤技術」を開発する。

Outline of Final Research Achievements

In recent years, significant advancements have been made in the development of bone replacement materials for osteogenesis, allowing for the healing of small bone defects. However, large bone defects remain a challenge. Human undifferentiated osteoblast-like cells (HAOB), established from human alveolar bone by the principal investigator, have demonstrated osteogenic potential in vivo.
In this project, we developed a protocol for collecting HAOBs using traceable raw materials, with the aim of progressing towards clinical application. Additionally, we discovered that HAOBs induce three-dimensional osteogenesis when combined with a three-dimensional structure of collagen and apatite. Our results indicate that HAOBs hold significant potential as a bone regenerative medicine product.

Academic Significance and Societal Importance of the Research Achievements

近年、急速に進歩を遂げた幹細胞・発生生物学の知見を駆使することで、様々な疾患に対する再生医療の実用化が可能になった。歯科領域においても間葉系幹細胞移植により垂直性骨欠損の再生医療の治療効果は既に確認されている。しかし現存の技術では水平性骨欠損を含む大型の骨欠損の再生には、従来技術における宿主の自己再生能力に期待する技術では困難であり、垂直方向に骨造成するための革新的な再生医療の技術開発が必要になる。本課題ではHAOBを用いた臨床応用可能な造骨細胞ー足場材の複合体の形成に成功し、また早期に水平性骨欠損部位に垂直方向への造骨を可能にする再生医療等製品として開発される可能性を示した。

Report

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

    (18 results)

All 2024 2023 2022 2021 Other

All Journal Article (10 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 9 results,  Open Access: 7 results) Presentation (7 results) (of which Int'l Joint Research: 4 results,  Invited: 3 results) Remarks (1 results)

  • [Journal Article] Public RNA-seq data-based identification and functional analyses reveal that MXRA5 retains proliferative and migratory abilities of dental pulp stem cells2023

    • Author(s)
      Yoshida Kazuma、Suzuki Shigeki、Yuan Hang、Sato Akiko、Hirata-Tsuchiya Shizu、Saito Masahiro、Yamada Satoru、Shiba Hideki
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 1-16

    • DOI

      10.1038/s41598-023-42684-z

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Autologous concentrated growth factor mediated accelerated bone healing in root-end microsurgery: A multicenter randomized clinical trial2023

    • Author(s)
      Yahata Yoshio、Handa Keisuke、Ohkura Naoto、Okamoto Motoki、Ohshima Jun、Itoh Shusaku、Kawashima Nobuyuki、Tanaka Toshinori、Sato Nobuya、Noiri Yuichiro、Hayashi Mikako、Okiji Takashi、Saito Masahiro
    • Journal Title

      Regenerative Therapy

      Volume: 24 Pages: 377-384

    • DOI

      10.1016/j.reth.2023.08.006

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Irrigation with reduced sodium hypochlorite solution concentration using laser‐induced cavitation is effective and safe in rat intraradicular biofilm model2023

    • Author(s)
      Uematsu Takehiro、Yahata Yoshio、Ohnishi Koyuki、Suzuki Shigeto、Kanehira Masafumi、Tanaka Toshinori、Sudo Susumu、Suresh Venkata Venkataiah、Saito Masahiro
    • Journal Title

      Australian Endodontic Journal

      Volume: 49 Issue: 3 Pages: 544-553

    • DOI

      10.1111/aej.12783

    • Related Report
      2023 Annual Research Report
  • [Journal Article] Salivary leukocyte esterase activity by SillHa is a risk indicator of periodontal disease2023

    • Author(s)
      Kyoko Ishii,Venkata Suresh Venkataiah,Takako Kajiwara,Kouta Umezawa,Shigeto Suzuki,Masato Nakano,Mayu Sawaguchi,Yoshio Yahata and Masahiro Saito
    • Journal Title

      BMC Oral Health

      Volume: 23 Issue: 1 Pages: 1-11

    • DOI

      10.1186/s12903-023-02874-7

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pharmacological Activation of YAP/TAZ by Targeting LATS1/2 Enhances Periodontal Tissue Regeneration in a Murine Mode2023

    • Author(s)
      Akiko Sato,Shigeki Suzuki,Hang Yuan,Rahmad Rifqi Fahreza,Xiuting Wang,Eiji Nemoto,Masahiro Saito and Satoru Yamada
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 24 Issue: 2 Pages: 970-970

    • DOI

      10.3390/ijms24020970

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A case series describing the risk of periodontal disease in Marfan syndrome patients harboring a possible aortic aneurysm or dissection2022

    • Author(s)
      Umezawa Kouta、Kajiwara Takako、Ishii Kyoko、Hasegawa Tatsuya、Suzuki Shigeto、Nakano Masato、Sawaguchi Mayu、Venkataiah Venkata Suresh、Yahata Yoshio、Ito Koki、Saiki Yoshikatsu、Saito Masahiro
    • Journal Title

      BMC Oral Health

      Volume: 22 Issue: 1 Pages: 336-336

    • DOI

      10.1186/s12903-022-02361-5

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Periodontal tissue regeneration by transplantation of autologous adipose tissue-derived multi-lineage progenitor cells2022

    • Author(s)
      Takedachi Masahide、Sawada Keigo、Sakura Kazuma、Morimoto Chiaki、Hirai Asae、Iwayama Tomoaki、Shimomura Junpei、Kawasaki Kohsuke、Fujihara Chiharu、Kashiwagi Yoichiro、Miyake Akimitsu、Yamada Tomomi、Okura Hanayuki、Matsuyama Akifumi、Saito Masahiro、Kitamura Masahiro、Murakami Shinya
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 8126-8126

    • DOI

      10.1038/s41598-022-11986-z

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Er:YAG laser-induced cavitation can activate irrigation for the removal of intraradicular biofilm2022

    • Author(s)
      Nagahashi Taiji、Yahata Yoshio、Handa Keisuke、Nakano Masato、Suzuki Shigeto、Kakiuchi Yusuke、Tanaka Toshinori、Kanehira Masafumi、Suresh Venkataiah Venkata、Saito Masahiro
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 4897-4897

    • DOI

      10.1038/s41598-022-08963-x

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Correction of large jawbone defect in the mouse using immature osteoblast-like cells and a 3D polylactic acid scaffold.2022

    • Author(s)
      Suzuki S, Venkataiah VS, Yahata Y, Kitagawa A, Inagaki M, Njuguna MM, Nozawa R, Kakiuchi Y, Nakano M, Handa K, Yamada M, Egusa H, Saito M.
    • Journal Title

      PNAS Nexus.

      Volume: 18 Issue: 4 Pages: 151-151

    • DOI

      10.1093/pnasnexus/pgac151

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical Applications of Cell-Scaffold Constructs for Bone Regeneration Therapy2021

    • Author(s)
      Venkataiah Venkata Suresh、Yahata Yoshio、Kitagawa Akira、Inagaki Masahiko、Kakiuchi Yusuke、Nakano Masato、Suzuki Shigeto、Handa Keisuke、Saito Masahiro
    • Journal Title

      Cells

      Volume: 10 Issue: 10 Pages: 2687-2687

    • DOI

      10.3390/cells10102687

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Regeneration of large jawbone defect using immature osteoblast like cells2024

    • Author(s)
      Masahiro Saito, Yuya Kamano, Futaba Harada, Yohio Yahata, Akira Kitagawa
    • Organizer
      Gordon Research Conference Bone and Teeth
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 3次元骨補填材を用いた新規骨再生法の探索2023

    • Author(s)
      鎌野優弥、原田芙太巴、八幡祥生、齋藤正寛
    • Organizer
      2023年秋季日本歯科保存学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Regeneration of large jaw bone defect in mice using complex of immatureosteoblast like cells and three dimensional polylactic acid scaffold withnanoscale architecture2023

    • Author(s)
      MasahiroSaito
    • Organizer
      International Symposium on Oral Health Sciences 2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Application of autologous concentrated growth factors(CGF) in endodontic microsurgery: A multi-center clinical trial2023

    • Author(s)
      Yoshio Yahata, Masahiro Saito
    • Organizer
      American Association of Endodontics 2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 未分化骨芽細胞と三次元高分子足場を用いた再生医療等製品の開発2022

    • Author(s)
      Venkataiah Venkata Sureshasa
    • Organizer
      2022年度秋季学術大会(第157回)
    • Related Report
      2022 Annual Research Report
  • [Presentation] Regeneration of large jaw bone defect in mice using complex of immature osteoblast like cells and three dimensional polylactic acid scaffold with nanoscale architecture2022

    • Author(s)
      Masahiro Saito
    • Organizer
      STOVITIMDEX
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ヒト歯槽骨由来未分化骨芽細胞および3次元ポリ乳酸足場材を用いた新規骨再生医療技術の開発2021

    • Author(s)
      齋藤正寛
    • Organizer
      日本歯科基礎医学会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Remarks] 骨細胞と足場材による大型顎骨欠損の再生に成功,新しい骨再生医療技術の開発

    • URL

      https://www.tohoku.ac.jp/japanese/2022/08/press20220825-02-mcob.html

    • Related Report
      2022 Annual Research Report

URL: 

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

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