Establishment of novel therapy for regeneration of periodontal ligament (PDL) by application of the angiogenic and hematopoietic activities of PDL-derived cells

• Project/Area Number: 26670852
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Dental engineering/Regenerative dentistry
• Research Institution: Iwate Medical University
• Principal Investigator: ISHISAKI Akira 岩手医科大学, 歯学部, 教授 (20356439)
• Co-Investigator(Kenkyū-buntansha): 藤原 尚樹 岩手医科大学, 歯学部, 准教授 (20190100)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: 歯根膜 / 血管内皮前駆細胞 / 血管新生 / 造血能力 / 歯周組織再生 / 間葉系幹細胞 / 血管形成 / 血球細胞分化

Outline of Final Research Achievements

Aim of this study is establishment of novel therapy for regeneration of periodontal ligament (PDL) by application of the angiogenic and hematopoietic activities of PDL-derived cells.
Here, we found that hypoxic condition strongly promoted angiogenic and hematopoietic activities of the PDL-derived endothelial progenitor cells (EPCs) in the three-dimensional culture system by using type I collagen gel, which possibly facilitates identification of key genes for the expression of angiogenic and hematopoietic activities of these cells. In addition, we found that cell-cell interaction between EPCs and nerve cells possibly enhanced angiogenic and hematopoietic activities of EPCs. There is a possibility that establishment of microcirculation therapy through application of EPC―nerve cell network for angiogenesis and hematopoiesis.

Research Products

• [Journal Article] SCRG1 suppresses LPS-induced CCL22 production through ERK1/2 activation in mouse macrophage Raw264.7 cells. (2017)
  • Author(s): Inoue M., Yamada J, Aomatsu-Kikuchi E., Satoh K., Kondo H., Ishisaki A., Chosa N.
  • Journal Title: Molecular Medicine Reports, in press. Volume: 1 Issue: 6 Pages: 1-8
  • DOI: 10.3892/mmr.2017.6492
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Enhancement of anti-inflammatory and osteogenic abilities of mesenchymal stem cells via cell-to-cell adhesion to periodontal ligament-derived fibroblasts. (2017)
  • Author(s): Suzuki, K., Chosa, N., Sawada, S., Takizawa, N., Yaegashi, T., and Ishisaki, A.
  • Journal Title: Stem Cells Int. Volume: 2017:3296498 Pages: 3296498-3296498
  • DOI: 10.1155/2017/3296498
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] PA-derived peptide, A6 is involved in the suppression of lipopolysaccaride-promoted inflammatory osteoclastogenesis and the resultant bone loss. (2017)
  • Author(s): Kanno, Y., Maruyama, C., Matsuda, A., and Ishisaki, A.
  • Journal Title: Immun. Inflamm. Dis. Volume: 印刷中
  • Peer Reviewed / Open Access
• [Journal Article] <b>Hertwig’s epithelial root sheath cells contribute to formation of periodontal ligament through epithelial-mesenchymal transition by </b><b>TGF-β </b> (2017)
  • Author(s): Itaya, S., Oka, K., Ogata, K., Tamura, S., Kira-Tatsuoka, M., Fujiwara, N., Otsu, K., Tsuruga, E., Ozaki, M., and Harada, H.
  • Journal Title: Biomedical Research Volume: 38 Issue: 1 Pages: 61-69
  • DOI: 10.2220/biomedres.38.61
  • NAID: 130005242923
  • ISSN: 0388-6107, 1880-313X
  • Peer Reviewed / Open Access
• [Journal Article] The blocking of uPAR suppresses lipopolysaccharide-induced inflammatory osteoclastogenesis and the resultant bone loss through attention of integrin β3/Akt pathway: The roles of uPAR in inflammatory bone loss. (2016)
  • Author(s): Kanno, Y., Ishisaki, A., Miyashita, M., and Matsuo, O.
  • Journal Title: Immun. Inflamm. Dis. Volume: 4 Issue: 3 Pages: 338-349
  • DOI: 10.1002/iid3.116
  • Peer Reviewed / Open Access
• [Journal Article] Establishment of mesenchymal stem cell lines derived from the bone marrow of GFP-transgenic mice exhibiting diversity in intracellular TGF-β and BMP signaling. (2016)
  • Author(s): Sawada, S., Chosa, N., Takizawa, N., Yokota, J., Igarashi, Y., Tomoda, K., Kondo, H., Yaegashi, T., and Ishisaki, A.
  • Journal Title: Mol. Med. Rep. Volume: 13 Issue: 3 Pages: 2023-2031
  • DOI: 10.3892/mmr.2016.4794
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Establishment of immortalized mesenchymal stem cells derived from the submandibular glands of tdTomato transgenic mice. (2015)
  • Author(s): Furukawa, S., Kuwajima, Y., Chosa, N., Satoh, K., Ohtsuka, M., Miura, H., Kimura, M., Inoko, H., Ishisaki, A., Fujimura, A., and Miura, H.
  • Journal Title: Exp. Ther. Med. Volume: 10 Issue: 4 Pages: 1380-1386
  • DOI: 10.3892/etm.2015.2700
  • NAID: 120006334507
  • Peer Reviewed / Open Access
• [Journal Article] Establishment of mesenchymal stem cell lines derived from the bone marrow of GFP-transgenic mice exhibiting diversity in intracellular TGF-β and BMP signaling. (2015)
  • Author(s): Sawada, S., Chosa, N., Takizawa, N., Yokota, J., Igarashi, Y., Tomoda, K., Kondo, H., Yaegashi, T., and Ishisaki, A.
  • Journal Title: Mol. Med. Rep. Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Tracking GFP-labeled transplanted mouse MSC in nude mice using in vivo fluorescence imaging. (2014)
  • Author(s): Taira, M., Hatakeyama, W., Yokota, J., Chosa, N., Ishisaki, A., Takafuji, K., Kihara, H., Kondo, H., Hattori, M.
  • Journal Title: Nano Biomed. Volume: 6 Pages: 73-77
  • NAID: 130005130560
  • Peer Reviewed
• [Presentation] 細胞特異的蛍光タンパク発現マウスと組織透明化を用いた組織3次元イメージング解析 (2016)
  • Author(s): 高橋颯、大津圭史、藤原尚樹、原田英光
  • Organizer: 岩手医科大学歯学会第42回総会
  • Place of Presentation: 岩手（盛岡）
  • Year and Date: 2016-12-03
• [Presentation] 歯周靭帯由来細胞における神経成長因子NGFの発現機構に関する研究 (2016)
  • Author(s): 太田 麻衣子、帖佐 直幸、客本 齊子、加茂 政晴、佐藤 健一、城 茂治、石崎 明
  • Organizer: 第３９回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-11-30
• [Presentation] 歯科材料からの微量溶出成分が間葉系幹細胞の骨芽細胞分化に与える影響 (2016)
  • Author(s): 根本 章、帖佐 直幸、客本 齊子、加茂 政晴、野田 守、石崎 明
  • Organizer: 第３９回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-11-30
• [Presentation] 間葉系幹細胞の抗炎症効果は歯根膜線維芽細胞との細胞間相互作用によって増強される (2016)
  • Author(s): 鈴木 啓太、帖佐 直幸、滝沢 尚希、客本 齊子、加茂 政晴、八重柏 隆、石崎 明
  • Organizer: 第３９回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-11-30
• [Presentation] 顎関節滑膜細胞による顎関節組織の線維化を促進する細胞内シグナル伝達機構について (2016)
  • Author(s): 横田 聖司、帖佐 直幸、衣斐 美歩、菊池 恵美子、木村 仁迪、客本 齊子、加茂 政晴、佐藤 和朗、石崎 明
  • Organizer: 第３９回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-11-30
• [Presentation] 歯肉線維芽細胞との細胞間相互作用は間葉系幹細胞の抗炎症作用を増強する (2015)
  • Author(s): 鈴木啓太、滝沢尚樹、帖佐直幸、客本斉子、加茂政晴、八重柏隆、石崎明
  • Organizer: 第３８回日本分子生物学会年会第８８回日本生化学会大会合同大会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2015-12-01
• [Presentation] 顎関節組織由来細胞におけるTGF-beta誘導性抗炎症性作用発現の調節機構を明らかにする研究 (2015)
  • Author(s): 横田聖司、帖佐直幸、衣斐美歩、菊池（青松）恵美子、木村仁迪、客本斉子、加茂政晴、三浦廣行、佐藤和朗、石崎明
  • Organizer: 第３８回日本分子生物学会年会第８８回日本生化学会大会合同大会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2015-12-01
• [Presentation] 成長因子が歯周靭帯由来血管内皮細胞株（EPC）の分化に与える影響について (2015)
  • Author(s): 木村仁迪、帖佐直幸、客本斉子、大久保直登、加茂政晴、佐藤和朗、石崎明
  • Organizer: 第３８回日本分子生物学会年会第８８回日本生化学会大会合同大会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2015-12-01
• [Presentation] 間葉系幹細胞由来ペプチドSCRG1はRANKL誘導性破骨細胞分化を抑制する (2015)
  • Author(s): 菊池（青松）恵美子、帖佐直幸、横田聖司、佐藤和朗、石崎明
  • Organizer: 第３８回日本分子生物学会年会第８８回日本生化学会大会合同大会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2015-12-01
• [Presentation] Establishment of a co-culture system for simultaneous proliferation of td-Tomato-expressing mouse bone marrow-derived mesenchymal stem cells and undifferentiated blood cells. (2014)
  • Author(s): Naoki Takizawa, Seiko Kyakumoto, Naoto Okubo, Naoyuki Chosa, Miho Ibi, Hideaki Fujiwara, Masaharu Kamo, Masato Otuka, Takashi Yaegashi , Akira Ishisaki.
  • Organizer: 第３７回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-11-25
• [Presentation] GFPマウス骨髄由来間葉系幹細胞の分化能とサイトカイン受容体の発現 (2014)
  • Author(s): 滝沢尚希, 澤田俊輔, 伊東俊太郎, 佐々木大輔, 帖佐直幸, 石崎明, 八重柏隆
  • Organizer: 第140回春季日本歯科保存学会
  • Place of Presentation: 滋賀県大津市
  • Year and Date: 2014-06-20