Tooth and periodontal tissue regeneration with purified mesenchymal stem cells and gene transfer technique

• Project/Area Number: 24792151
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Dental engineering/Regenerative dentistry
• Research Institution: Tohoku University (2014-2015); Keio University (2012-2013)
• Principal Investigator: Niibe Kunimichi 東北大学, 大学病院, 助教 (50468500)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 間葉系幹細胞 / 歯胚再生 / 再生医療 / 歯原性上皮 / 歯原性間葉 / iPS細胞 / 歯牙再生 / 遺伝子導入

Outline of Final Research Achievements

The cultivable mesenchymal stem cell (MSC) has self-renewal competence. However, self-renewal ability of MSC shows a decrease after several passages using adhesion culture system. In addition, differentiation advancing and cell phenotype changing also appear in MSC after long term culture using the conventional adhesion culture. It is necessary to multiply the purified MSC in vitro without losing their stem-ness for their use in tooth germ reproduction. Therefore, establish a new culture method to maintain the stem-ness of the MSC is imperative.
Currently applicant to maintain the undifferentiated MSCs in a particular environment. Further, this culture method could be resurrected undifferentiated stage. This method can maintain the stem-ness of MSC through forming a three-dimensional cell mass. This research is delayed from the plan, but now, it is carried out to continue the research for the realization of the tooth germ and periodontal tissue regeneration using this cell mass.

Research Products

• [Journal Article] Controlled Osteogenic Differentiation of Mouse Mesenchymal Stem Cells by Tetracycline-Controlled Transcreptional Activation of Amelogenin (2015)
  • Author(s): 9.Wang F, Okawa H, Kamano Y, Niibe K, Kayashima H, Osathanon T, Pavasant P, Saeki M, Yatani H, Egusa H
  • Journal Title: PloS One Volume: 10(12) Issue: 12 Pages: e0145677-e0145677
  • DOI: 10.1371/journal.pone.0145677
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Purified Human Dental Pulp Stem Cells Promote Osteogenic Regeneration. (2015)
  • Author(s): Yasui T, Mabuchi Y, Toriumi H, Ebine T, Niibe K, Houlihan DD, Morikawa S, Onizawa K, Kawana H, Akazawa C, Suzuki N, Nakagawa T, Okano H, Matsuzaki Y.
  • Journal Title: journal of Dental Research Volume: 95 Issue: 2 Pages: 206-214
  • DOI: 10.1177/0022034515610748
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Osteonecrosis of the jaw in patients with dental prostheses being treated with bisphosphonates or denosumab (2015)
  • Author(s): Niibe K, Ouchi T, Iwasaki R, Nakagawa T, Horie N.
  • Journal Title: Journal of Prosthodontic Research Volume: 59 Issue: 1 Pages: 3-5
  • DOI: 10.1016/j.jpor.2014.08.001
  • NAID: 130007936677
  • ISSN: 1883-1958, 1883-9207
  • Peer Reviewed / Open Access
• [Journal Article] LNGFR(+)THY-1(+)VCAM-1(hi+) Cells Reveal Functionally Distinct Subpopulations in Mesenchymal Stem Cells. (2013)
  • Author(s): 1. Mabuchi Y, Morikawa S, Harada S, Niibe K, Suzuki S, Renault-Mihara F, Houlihan DD, Akazawa C, Okano H, Matsuzaki Y
  • Journal Title: Stem Cell Reports. Volume: 1(2) Pages: 152-165
  • Peer Reviewed
• [Journal Article] Isolation of mouse mesenchymal stem cells on the basis of expression of Sca-1 and PDGFR-α (2012)
  • Author(s): Houlihan DD, Mabuchi Y, Morikawa S, Niibe K, Araki D, Suzuki S, Okano H, Matsuzaki Y.(These authors contributed equally to this work.)
  • Journal Title: Nat Protoc Volume: 7(12) Issue: 12 Pages: 2103-2111
  • DOI: 10.1038/nprot.2012.125
  • Peer Reviewed
• [Presentation] 6.Potential of purified mesenchymal stem cells for regenerative dentistry (2015)
  • Author(s): Kunimichi Niibe
  • Organizer: Chulalongkorn-Tohoku Joint Symposium in Dental Science 2015
  • Place of Presentation: タイ バンコク
  • Year and Date: 2015-12-09
  • Int'l Joint Research / Invited
• [Presentation] 2.「再生歯科補綴」の技術確立に向けて ―補綴歯科治療に求められる歯・歯槽骨の再生とは－ (2015)
  • Author(s): 新部邦透
  • Organizer: 第124回日本補綴歯科学会
  • Place of Presentation: 大宮ソニックシティ・大宮市
  • Year and Date: 2015-05-30
  • Invited
• [Presentation] 間葉系幹細胞純化技術の再生歯科医療への応用 (Application of purified mesenchymal stem cells to regenerative dentistry) (2015)
  • Author(s): 新部邦透，江草宏
  • Organizer: 第4回補綴若手研究会
  • Place of Presentation: 熱海ホテルニューアカオ，熱海
  • Year and Date: 2015-03-21 – 2015-03-22
• [Presentation] ヒトiPS細胞由来神経堤細胞群における効率的な純化間葉系幹細胞の回収 (2015)
  • Author(s): 黄地健仁，森川暁，新部邦透，奥野博庸，赤松和土，中川種昭，岡野栄之
  • Organizer: 第１４回日本再生医療学会総会
  • Place of Presentation: パシフィコ横浜，横浜
  • Year and Date: 2015-03-19 – 2015-03-21
• [Presentation] 欠損歯補綴物を有するビスフォスフォネート製剤及びデノスマブ投与者の臨床統計 (2014)
  • Author(s): 黄地健仁，新部邦透，岩崎良太郎，有馬誠亮，龍留美子，鈴木啓介，鈴木潔，中川種昭，堀江伸行
  • Organizer: 公益社団法人日本補綴歯科学会東京支部総会第１８回学術大会
  • Place of Presentation: 昭和大学旗の台キャンパス，東京
  • Year and Date: 2014-11-09
• [Presentation] 中胚葉系細胞を起源とする間葉系幹細胞の分化能 (2013)
  • Author(s): 新部邦透, 森川暁, 中川種昭
  • Organizer: 第６７回NPO法人日本口腔科学会学術集会
  • Place of Presentation: 宇都宮
• [Presentation] ヒト間葉系幹細胞の予期的分離と機能解析 (2013)
  • Author(s): 森川暁, 馬淵洋, 新部邦透, 松崎有未, 岡野栄之, 河奈裕正, 中川種昭
  • Organizer: 第６７回NPO法人日本口腔科学会学術集会
  • Place of Presentation: 宇都宮
• [Presentation] 臨床応用へ向けた間葉系幹細胞の分離とiPS細胞の高品質化 (2012)
  • Author(s): 新部 邦透、堀江 伸行、鈴木 潔、鈴木 啓介、池田 浩子、西山 留美子、有馬 誠亮、中川 種昭
  • Organizer: 社団法人日本補綴歯科学会第１２１回学術大会
  • Place of Presentation: 横浜