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Investigation of differentiation control from human embryonic stem cells to responsible cells for periodontal regeneration

Research Project

Project/Area Number 18H02985
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 57040:Regenerative dentistry and dental engineering-related
Research InstitutionTokyo Medical and Dental University (2019-2021)
Tokyo Women's Medical University (2018)

Principal Investigator

Iwata Takanori  東京医科歯科大学, 大学院医歯学総合研究科, 教授 (60431946)

Co-Investigator(Kenkyū-buntansha) 中井 謙太  東京大学, 医科学研究所, 教授 (60217643)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2021: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2019: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2018: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
KeywordsES細胞 / 間葉系幹細胞 / 歯根膜由来間葉系幹細胞 / 細胞治療 / 歯周組織再生 / 神経堤細胞 / 分化制御 / 歯周病 / 歯根膜細胞 / 分化誘導 / iPS細胞 / 再生医療 / 細胞分化 / ES/iPS細胞 / 細胞ソース / ヒトES細胞
Outline of Final Research Achievements

In this study, we developed technologies for efficient differentiation of pluripotent stem cells, human ES cells, into neural crest cells, and also for efficient differentiation of neural crest cells into mesenchymal stem cells. Although induction of differentiation into neural crest cells has been established to some extent, various extracellular matrices were used to achieve even higher efficiency. By using a certain extracellular matrix, we determined the culture conditions under which neural crest cells can be induced more efficiently than in the past. Differentiation of neural crest cells into mesenchymal stem cells was performed using conventional methods. By comparing the results of transcriptome analysis of these cells with those of the PDL-MSCs already maintained in our laboratory, we obtained an index of the genetic profile of cells suitable for periodontal tissue regeneration.

Academic Significance and Societal Importance of the Research Achievements

歯周病は、本邦において歯を失う最大の原因である。我々は、歯科領域で日常的に抜歯されている親知らずなどの不働歯から歯根膜由来間葉系幹細胞(PDL-MSC)を単離し、重度歯周病患者の治療に応用することで、その安全性と有効性を示してきた。本研究では、無限の増殖能を持つヒトES細胞に着目し、ES細胞から最終分化産物であるPDL-MSCを分化誘導するための手法とその過程を詳細に検討することにより、ES細胞由来PDL-MSCを臨床応用するための基礎医学的知見を得た。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (39 results)

All 2022 2021 2020 2019 2018 Other

All Journal Article (20 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 20 results,  Open Access: 18 results) Presentation (12 results) (of which Int'l Joint Research: 6 results,  Invited: 5 results) Book (4 results) Remarks (2 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] First-in-human autologous oral mucosal epithelial sheet transplantation to prevent anastomotic re-stenosis in congenital esophageal atresia2022

    • Author(s)
      Fujino A, Fuchimoto Y, Baba Y, Isogawa N, Iwata T, Arai K, Abe M, Kanai N, Takagi R, Maeda M, Umezawa A.
    • Journal Title

      Stem Cell Research & Therapy

      Volume: 13(1) Issue: 1 Pages: 35-35

    • DOI

      10.1186/s13287-022-02710-9

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Antioxidant effect of enamel matrix derivative for early phase of periodontal tissue regeneration in diabetes2022

    • Author(s)
      Takeda Kohei、Mizutani Koji、Matsuura Takanori、Kido Daisuke、Mikami Risako、Buranasin Prima、Saito Natsumi、Kominato Hiromi、Takemura Shu、Nakagawa Keita、Iwata Takanori
    • Journal Title

      Journal of Periodontology

      Volume: - Issue: 8 Pages: 1206-1217

    • DOI

      10.1002/jper.21-0413

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Single cell RNA sequencing reveals critical functions of Mkx in periodontal ligament homeostasis.2022

    • Author(s)
      Takada K, Chiba T, Miyazaki T, Yagasaki L, Nakamichi R, Iwata T, Moriyama K, Harada H, Asahara H.
    • Journal Title

      Front Cell Dev Biol

      Volume: 4 Pages: 1-13

    • DOI

      10.3389/fcell.2022.795441

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Synergy of molecularly mobile polyrotaxane surfaces with endothelial cell co-culture for mesenchymal stem cell mineralization2021

    • Author(s)
      Masuda Hiroki、Arisaka Yoshinori、Hakariya Masahiro、Iwata Takanori、Yoda Tetsuya、Yui Nobuhiko
    • Journal Title

      RSC Advances

      Volume: 11 Issue: 30 Pages: 18685-18692

    • DOI

      10.1039/d1ra01296g

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Alloplastic Bone Substitutes for Periodontal and Bone Regeneration in Dentistry: Current Status and Prospects2021

    • Author(s)
      Fukuba Shunsuke、Okada Munehiro、Nohara Kohei、Iwata Takanori
    • Journal Title

      Materials

      Volume: 14 Issue: 5 Pages: 1096-1096

    • DOI

      10.3390/ma14051096

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of Low-Level Er:YAG Laser Irradiation on Proliferation and Calcification of Primary Osteoblast-Like Cells Isolated From Rat Calvaria2020

    • Author(s)
      Niimi Hiromi、Ohsugi Yujin、Katagiri Sayaka、Watanabe Kazuki、Hatasa Masahiro、Shimohira Tsuyoshi、Tsuchiya Yosuke、Maekawa Shogo、Hirota Tomomitsu、Kadokura Hiroshi、Yokose Satoshi、Iwata Takanori、Aoki Akira
    • Journal Title

      Frontiers in Cell and Developmental Biology

      Volume: 8 Pages: 459-459

    • DOI

      10.3389/fcell.2020.00459

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Accuracy of cone beam computed tomography in evaluation of palatal mucosa thickness.2020

    • Author(s)
      Ogawa M, Katagiri S, Koyanagi T, Maekawa S, Shiba T, Ohsugi Y, Takeuchi Y, Ikawa T, Takeuchi S, Sekiuchi T, Arai Y, Kazama R, Wakabayashi N, Izumi Y, Iwata T.
    • Journal Title

      J Clin Periodontol.

      Volume: 4 Issue: 4 Pages: 479-488

    • DOI

      10.1111/jcpe.13254

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] rhBMP-2 Pre-Treated Human Periodontal Ligament Stem Cell Sheets Regenerate a Mineralized Layer Mimicking Dental Cementum2020

    • Author(s)
      Park Joo-Young、Park Chan Ho、Yi TacGhee、Kim Si-na、Iwata Takanori、Yun Jeong-Ho
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 11 Pages: 3767-3767

    • DOI

      10.3390/ijms21113767

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Co-cultured spheroids of human periodontal ligament mesenchymal stem cells and vascular endothelial cells enhance periodontal tissue regeneration2020

    • Author(s)
      Sano Kotaro、Usui Michihiko、Moritani Yuki、Nakazawa Kohji、Hanatani Tomoya、Kondo Hisataka、Nakatomi Mitsushiro、Onizuka Satoru、Iwata Takanori、Sato Tsuyoshi、Togari Akifumi、Ariyoshi Wataru、Nishihara Tatsuji、Nakashima Keisuke
    • Journal Title

      Regenerative Therapy

      Volume: 14 Pages: 59-71

    • DOI

      10.1016/j.reth.2019.12.008

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] PCR detection and new therapies for COVID-192020

    • Author(s)
      Iwata Takanori
    • Journal Title

      Journal of Periodontal & Implant Science

      Volume: 50 Issue: 3 Pages: 133-133

    • DOI

      10.5051/jpis.2020.50.3.133

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] RNA-sequencing reveals positional memory of multipotent mesenchymal stromal cells from oral and maxillofacial tissue transcriptomes2020

    • Author(s)
      Onizuka Satoru、Yamazaki Yasuharu、Park Sung-Joon、Sugimoto Takayuki、Sone Yumiko、Sj?qvist Sebastian、Usui Michihiko、Takeda Akira、Nakai Kenta、Nakashima Keisuke、Iwata Takanori
    • Journal Title

      BMC Genomics

      Volume: 21 Issue: 1 Pages: 417-417

    • DOI

      10.1186/s12864-020-06825-2

    • NAID

      120007175430

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Characterization of proliferation, differentiation potential, and gene expression among clonal cultures of human dental pulp cells.2020

    • Author(s)
      Kobayashi T, Torii D, Iwata T, Izumi Y, Nasu M, Tsutsui TW.
    • Journal Title

      Human Cell

      Volume: - Issue: 3 Pages: 1-12

    • DOI

      10.1007/s13577-020-00327-9

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] In Vitro Cytological Responses against Laser Photobiomodulation for Periodontal Regeneration2020

    • Author(s)
      Ohsugi Yujin、Niimi Hiromi、Shimohira Tsuyoshi、Hatasa Masahiro、Katagiri Sayaka、Aoki Akira、Iwata Takanori
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 23 Pages: 9002-9002

    • DOI

      10.3390/ijms21239002

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Allogeneic multipotent mesenchymal stromal cell sheet transplantation promotes healthy healing of wounds caused by zoledronate and dexamethasone in canine mandibular bones2019

    • Author(s)
      KAIBUCHI Nobuyuki†, IWATA Takanori, ONIZUKA Satoru, YANO Kosei, TSUMANUMA Yuka, YAMATO Masayuki, OKANO Teruo, ANDO Tomohiro
    • Journal Title

      Regenerative Therapy

      Volume: 10 Pages: 77-83

    • DOI

      10.1016/j.reth.2018.10.008

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Application of Periodontal Ligament-Derived Multipotent Mesenchymal Stromal Cell Sheets for Periodontal Regeneration.2019

    • Author(s)
      Onizuka S, Iwata T.
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 20 Issue: 11 Pages: 2796-2796

    • DOI

      10.3390/ijms20112796

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Oral keratinocyte-derived exosomes regulate proliferation of fibroblasts and epithelial cells2019

    • Author(s)
      Sjoqvist Sebastian、Kasai Yoshiyuki、Shimura Daisuke、Ishikawa Taichi、Ali Nadiah、Iwata Takanori、Kanai Nobuo
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 514 Issue: 3 Pages: 706-712

    • DOI

      10.1016/j.bbrc.2019.04.202

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A systematic sequencing-based approach for microbial contaminant detection and functional inference.2019

    • Author(s)
      Park SJ, Onizuka S, Seki M, Suzuki Y, Iwata T, Nakai K.
    • Journal Title

      BMC Biology

      Volume: 13 Issue: 1 Pages: 72-72

    • DOI

      10.1186/s12915-019-0690-0

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Exosomes derived from clinical-grade oral mucosal epithelial cell sheets promote wound healing2019

    • Author(s)
      Sjoqvist Sebastian、Ishikawa Taichi、Shimura Daisuke、Kasai Yoshiyuki、Imafuku Aya、Bou-Ghannam Sophia、Iwata Takanori、Kanai Nobuo
    • Journal Title

      Journal of Extracellular Vesicles

      Volume: 8 Issue: 1 Pages: 1565264-1565264

    • DOI

      10.1080/20013078.2019.1565264

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Periodontal regeneration with autologous periodontal ligament-derived cells sheets - A safety and efficacy study in ten patients.2018

    • Author(s)
      Iwata T, Yamato M, Washio K, Yoshida T, Tsumanuma Y, Yamada A, Onizuka S, Izumi Y, Ando T, Okano T, Ishikawa I.
    • Journal Title

      Regenerative Therapy

      Volume: 9 Pages: 38-44

    • DOI

      10.1016/j.reth.2018.07.002

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Spheroid culture enhances osteogenic potential of periodontal ligament mesenchymal stem cells2018

    • Author(s)
      Moritani Y.、Usui M.、Sano K.、Nakazawa K.、Hanatani T.、Nakatomi M.、Iwata T.、Sato T.、Ariyoshi W.、Nishihara T.、Nakashima K.
    • Journal Title

      Journal of Periodontal Research

      Volume: 53 Issue: 5 Pages: 870-882

    • DOI

      10.1111/jre.12577

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] 結紮誘導歯周炎モデルマウスを用いたダイオードレーザー照射による歯周炎抑制効果2022

    • Author(s)
      大杉勇人、畑佐将宏、下平剛、芝多佳彦、駒津匡二、土谷洋輔、福場駿介、新見ひろみ、森田和機、片桐さやか、岩田隆紀、青木章
    • Organizer
      第33回日本レーザー歯学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 細胞シート技術を用いた歯周組織の再生2022

    • Author(s)
      岩田隆紀
    • Organizer
      第5回大型医療研究推進フォーラム
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Low-level Er:YAG laser irradiation induced alteration of gene expression in rat calvarial osteogenic cells2021

    • Author(s)
      Shimohira T, Niimi H, Ohsugi Y, Tsuchiya Y, Morita K, Yoshida S, Hatasa M, Shiba T, Kadokura H, Yokose S, Katagiri S, Iwata T, Aoki A.
    • Organizer
      Dental Laser Virtual Scientific Conference 2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Sequential microarray analysis of Er:YAG laser ablated bone tissue2021

    • Author(s)
      Ohsugi Y, Katagiri S, Niimi H, Hatasa M, Watanabe K, Shimohira T, Mizutani K, Kadokura H, Yokose S, Iwata T, Aoki A
    • Organizer
      The 99th General Session of the IAD
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 国際セッション「歯周組織再生療法の変遷と細胞治療」2021

    • Author(s)
      岩田隆紀
    • Organizer
      第24回日本歯科医学会学術大会
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Porphyromonas gingivalisは妊娠中の母体の肥満と胎仔の低体重を引き起こす2021

    • Author(s)
      吉田澄子、畑佐将宏、片桐さやか、大杉勇人、土谷洋輔、新見ひろみ、下平剛、劉安豪、森田和機、佐々木直樹、前川祥吾、芝多佳彦、新田 浩、岩田 隆紀
    • Organizer
      第64回秋季日本歯周病学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 歯周病と令和時代の口腔セルフケア2021

    • Author(s)
      岩田隆紀
    • Organizer
      第64回秋季日本歯周病学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Periodontal Regeneration with Cell Sheet Technology2020

    • Author(s)
      Takanori Iwata
    • Organizer
      106th Annual Meeting of American Academy of Periodontology
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 同種歯根膜由来間葉系幹細胞シートによる歯周組織の再生2019

    • Author(s)
      岩田隆紀
    • Organizer
      第1 回細胞シート工学イノベーションフォーラム
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Periodontal Regeneration with Periodontal Ligament Derived Multipotent Mesenchymal Stromal Cell Sheets2018

    • Author(s)
      Iwata Takanori
    • Organizer
      2018 KAP General Session
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Regenerative potential of exosomes isolated from clinical grade oral mucosal epithelial cell sheet production2018

    • Author(s)
      Sjoqvist Sebastian JF, ISHIKAWA Taichi, SHIMURA Daiske, KASAI Yoshiyuki, ONIZUKA Satoru, IMAFUKU Aya, OKADA Ryo, IWATA Takanori, TAKAHASHI Akiko, KANAI Nobuo
    • Organizer
      5th TERMIS-World Congress 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The establishment of safety and efficacy evaluation for allogeneic periodontal ligament-derived multipotent mesenchymal stromal cell sheetwith next-generation sequencer2018

    • Author(s)
      Iwata Takanori, Onizuka Satoru, Park Sung-Joon, Tsumanuma Yuka, Nakai Kenta, Izumi Yuichi, Ando Tomohiro
    • Organizer
      5th TERMIS World Congress 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Book] 歯科衛生士・歯科助手 おしごとハンドブック2022

    • Author(s)
      岩田隆紀、水谷幸嗣、岩野義弘、松浦孝典
    • Total Pages
      256
    • Publisher
      クインテッセンス出版
    • ISBN
      9784781208602
    • Related Report
      2021 Annual Research Report
  • [Book] 月刊糖尿病 特集 糖尿病とNAFLD/NASH2021

    • Author(s)
      畑佐将宏、吉田澄子、片桐さやか、岩田隆紀
    • Total Pages
      9
    • Publisher
      テルモ株式会社
    • Related Report
      2021 Annual Research Report
  • [Book] Pharma Media 特集 再生医療への期待ー各疾患領域における現状と展望2021

    • Author(s)
      岩田隆紀
    • Total Pages
      3
    • Publisher
      メディカルレビュー社
    • Related Report
      2021 Annual Research Report
  • [Book] 再生医療・細胞医療の研究と産業化の最前線2018

    • Author(s)
      先進医療フォーラム
    • Total Pages
      93
    • Publisher
      日本医学出版
    • ISBN
      9784865770308
    • Related Report
      2018 Annual Research Report
  • [Remarks] 東京医科歯科大学歯周病学分野

    • URL

      https://www.tmd.ac.jp/dent/peri/peri-J.htm

    • Related Report
      2021 Annual Research Report
  • [Remarks] 研究者データベース

    • URL

      https://reins.tmd.ac.jp/html/100025631_ja.html

    • Related Report
      2021 Annual Research Report
  • [Patent(Industrial Property Rights)] 組織再生細胞シート、製造方法及びその利用方法2021

    • Inventor(s)
      森田和機、坂井秀昭、岩田隆紀、岡野光夫
    • Industrial Property Rights Holder
      森田和機、坂井秀昭、岩田隆紀、岡野光夫
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2021-188106
    • Filing Date
      2021
    • Related Report
      2021 Annual Research Report

URL: 

Published: 2018-04-23   Modified: 2023-01-30  

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