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Bone regeneration therapy using HAp/Cot with MSC.

Research Project

Project/Area Number 13557125
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Orthopaedic surgery
Research InstitutionTokyo Medical and Dental University

Principal Investigator

SHINOMIYA Kenichi  Tokyo Medical and Dental University, Graduate School, Professor, 大学院・医歯学総合研究科, 教授 (20111594)

Co-Investigator(Kenkyū-buntansha) KURODA Hiroshi  Tokyo Medical and Dental University, Graduate School, Assistant, 大学院・医歯学総合研究科, 助手 (70282746)
ITO Soichiro  Tokyo Medical and Dental University, Human Gene Science Center, Associate Professor, 疾患遺伝子実験センター, 助教授 (10242190)
KOMORI Hiromichi  Tokyo Medical and Dental University, Graduate School, Associate Professor, 大学院・医歯学総合研究科, 助教授 (60262169)
波呂 浩孝  東京医科歯科大学, 大学院・医歯学総合研究科, 助手 (10313264)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2003: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2002: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2001: ¥8,700,000 (Direct Cost: ¥8,700,000)
KeywordsHAp / Col / MSC / Sccaffold of MSC / Porous HAp / bone formation capability / clinical / 臨床治験 / ヒト骨髄間葉系細胞 / アルカリフォスファターゼ / 霊長類 / 多血小板血漿 / 3元 / 連通孔 / 企業化 / ヒト骨髄培養細胞 / β-TCP / 細胞治療センター / 骨再生 / 多孔体HAp / 生体吸収性 / BMP2担体 / サル・ヒト骨髄間葉系細胞
Research Abstract

When we started this study, hydroxyapatite/collagen nanocomposite (HAp/Col), which is an artificial bone incorporated into bone remodeling processes, had been developed. And tissue engineering with human mesenchymal stern cells (MS Cs)had been developed for clinical use of bone reconstruction. The purpose of this study was to develop the bone regeneration system using HAp/Col combined with MSC.
At the beginning of this study, there had been only a dense block of HAp/Col, and it was not suitable or using as scaffold of MSC. For this reason or others, we, tried to develop some forms of HAp/Col. Porous HAp/Col is the most desirable as a scaffold of MSC among varieties of the HAp/Col implants developed in this study. In addition, the porous body of HAp/Col has also more favorable characteristics as artificial bone than the other forms of HAp/Cot implants. The development of the porous HAp/Col is ongoing, aiming to be a commercialized product.
During this study, we had to study bone formation ability of MSC/scaffold hybrids without HAp/Col because porous HAp/Col had been under development 'Porous β-TCP (commercial product) was selected as the scaffold of MSC. We confirmed the bone formation ability of human MSC, but there were significant differences of theability among donors. A clinical application model of bone regeneration with MSC was also tested using the lumbar posterolateral fusion (PLF) model of monkey. PLF is one of the most difficult model to obtain successful results because the formed bone bridging transverse processes is ectopic bone and it must have enough strength to bear mechanical stresses from various directions. The results we obtained from the monkeys' PLF using MSC/β-TCP hybrids were superior to the conventional method using autograft bone. It would indicate the possibility that the use of MSC/β-TCP hybrids in clinical application is superior to conventional autograft bone.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] Itoh S., Kikuchi M., Takakuda K., Koyama Y., Matsumoto H.N., Tanaka J., Shinomiya K.: "The biocompatibility and osteoconductive activity of a novel hydroxyapatite/collagen composite biomaterial, and its function as a carrier of rhBMP-2."J.Biomed.Mater.Res.. 54. 445-453 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shinomiya K., Itoh S., Kawauchi T., Kikuchi M., Tanaka J: "Development of a novel hydroxyapatite/colagen composite biomaterial."Tissue Engineering for Therapeutic Use. 5. 165-177 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kikuchi M., Itoh S., Ichinose S., Shinomiya K., Tanaka J.: "Self-Organization Mechanism in a Bone-like Hydroxyapatite/Collagen Nanocomposite Syntheasized in vitro and Its Biological Reaction in vivo."Biomaterials. 22. 1705-1711 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Itoh S., Kikuchi M., Takakuda K., Nagaoka K., Koyama Y., Tanaka J., Shinomiya K.: "Implantation study of a novel Hydroxyapatite/Collagen (HAp/Col) composite into weight-bearing sites of dogs."J.Biomed.Mater.Res.. 63. 507-515 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Itoh S., Kikuchi M., Koyama Y., Takakuda K., Shinomiya K., Tanaka J.: "Development of an artificial vertebral body using a novel biomaterial, Hydroxyapatite/Collagen composite."Biomaterials. 23. 3919-3926 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Saotome S., Uemura T., Kikuchi M., Itoh S., Takakuda K., Tanaka J., Shinomiya K.: "In Vitro Evaluation of Highly Absorptive Ceramics Materials Needs Consideration of Calcium and Magnesium Ions Adsorbed to the Materials."Key-Engineering Materials. 218-220. 153-156 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kikuchi M., Itoh S., Matsumoto H.N., Takakuda K., Shinomiya K., Tanaka J.: "Fibrillogenesis of Hydroxyapatite/Collagen Self-Organized Composites."Key-Engineering Materials. 240-242. 567-570 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kikuchi M., Ikoma T., Syoji D., Matsumoto H.N., Itoh S., Takakuda K., Shinomiya K.: "Porous Body Preparation of Hydroxyapatite/Collagen Nanocomposites for Bone"Key-Engineering Materials. 254-256. 561 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Itoh S., Kikuchi M., Kiyama Y., Matsumoto H.N., Takakuda K., Shinomiya K., Tanaka J.: "Development of a novel biomaterial, hydroxyapatite/collagen (HAp/Col) composite for medical use."Bio-Med.Mater.Eng.. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Itoh S., Kikuchi M., Takakuda K., Koyama Y., Matsumoto H.N., Ichinose S., Tanaka J., Kawauchi I., Shinomiya K.: "The biocompatibility and osteoconductive activity of a novel hydroxyapatite/collagen composite biomaterial, and its function as a carrier of rhBMP-2."J.Biomed.Mater.Res.. 54. 445-453 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shinomiya K., Itoh S., Kawauchi T., Kikuchi M., Tanaka J.: "Development of a novel hydroxyapatite/collagen composite biomaterial."Tissue Engineering for Therapeutic Use. 2. 165-177 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kikuchi M., Itoh S., Ichinose S., Shinomiya K., Tanaka J.: "Self-Organization Mechanism in a Bone-like Hydroxyapatite / Collagen Nanocomposite Synthesized in vitro and Its Biological Reaction in vivo."Biomaterials. 22. 1705-1711 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Itoh S., Kikuchi M., Takakuda K., Nagaoka K., Koyama Y., Tanaka J., Shinomiya K.: "Implantation study of a novel Hydroxyapatite/Collagen (HAp/Col) composite into weight-bearing sites of dogs."J.Biomed.Mater.Res,: Applied Biomaterials. 63. 507-515 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Itoh S., Kikuchi M., Koyama Y., Takakuda K., Shinomiya K., Tanaka J.: "Development of an artificial vertebral body using a novel biomaterial, Hydroxyapatite/Collagen composite."Biomaterials. 23. 3919-3926 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sotome S., Uemura T., Kikuchi M., Itoh S., Takakuda K., Tanaka J., Takahashi M., Tateishi T., Shinomiya K.: "In Vitro Evaluation of Highly Absorptive Ceramics Materials Needs Consideration of Calcium and Magnesium Ions Adsorbed to the Materials."Key-Engineering Materials. 218-220. 153-156 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kikuchi M., Itoh S., Matsumoto H.N., Koyama, Y., Takakuda K., Shinomiya, K., Tanaka J.: "Fibrillogens is of Hydroxyapatite/Collagen Self-Organized Composites."Key-Engineering Materials. 240-242. 567-570 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kikuchi M., Ikoma T., Syoji D., Matsumoto H.N., Koyama, Y., Itoh S., Takakuda K., Shinomiya, K., Tanaka J.: "Porous Body Preparation of Hydroxyapatite/Collagen Nanocomposites for Bone T issue Regeneration."Key-Engineering Materials. 254-256. 561-564 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Itoh S., Kikuchi M., Koyama Y., Matsumoto H.N., Takakuda K., Shinomiya K., Tanaka J.: "Development of a novel biomaterial, hydroxyapatite/collagen (HAp/Col) composite for medical use."Bio-Med: Mater.Eng.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] S.Sotome, T.Uemura, S.Itoh, M.Kikuchi, J.Tanaka, T.Tateishi, K.Shinomiya: "Synthesis and in vivo evaluation of a novel Hydroxyapatite/Collagen-alginate as a bone filler and a drug delivery carrier of bone morphogenetic protein"Materials Science and Engineering : C. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Nakamura H, Kumei Y, Morita S, Shimokawa H, Ohya K, Shinomiya K.: "Suppression of osteoblastic phenotypes and modulation of pro- and anti-apoptotic features in normal human osteoblastic cells under a vector-averaged gravity condition."Journal of Medical and Dental Science. 50(2). 167-176 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yagi K, Tsuji K, Nifuji A, Shinomiya K, Nakashima K, DeCrombrugghe B, Noda M.: "Bone morphogenetic protein-2 enhances osterix gene expression in chondrocytes."Journal of cellular biochemistry. 88(6). 1077-1083 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 田中順三, 四宮謙一(その他): "再生医療-ティッシュエンジニアリング&生体材料 最前線"日刊工業新聞社. 160 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] S.Sotome, T.Uemura, S.Itoh, M.Kikuchi, J.Tanaka, T.Tateishi, K.Shinomiya: "Synthesis and in vivo evaluation of a novel Hydroxyapatite/Collagen-alginate as a bone filler and a drug delivery carrier of bone morphogenetic protein"Materials Science and Engineering : C. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] S.Itoh, M.Kikuchi, K.Takakuda, K Nagaoka, Y.Koyama, J.Tanaka K.Shinomiya: "Implantation study of a Novel hydroxyapatite/collagen composite into weight-bearing sites of dogs"J Biomed Mater Res. 63. 507-515 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] S Itoh, M Kikuchi, Y Koyama, J Tanaka, K Shinomiya: "Development of an artificial vertebral body using a novel biomaterial, hydroxyapatite/collagen composite"Biomaterial. 23. 3919-3926 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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