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Regeneration of Bone and Cartilage by a Novel 3-D Culture System Based on Formation of Vascutar Network

Research Project

Project/Area Number 14370658
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Surgical dentistry
Research InstitutionThe University of Tokyo

Principal Investigator

TAKATO Tsuyoshi  The University of Tokyo, Faculty of Medicine, Oral Surgery, Professor, 医学部附属病院, 教授 (90171454)

Co-Investigator(Kenkyū-buntansha) TATEISHI Tetsuya  The University of Tokyo, School of Science and Engineering, Professor, 理工学部, 教授 (40323521)
HIKIJI Hisako  The University of Tokyo, Health Service Center, Lecturer, 保健センター, 講師 (50292876)
MORI Yoshiyuki  The University of Tokyo, Faculty of Medicine, Oral Surgery, Lecturer, 医学部附属病院, 講師 (70251296)
UCHIDA Takashi  The University of Tokyo, School of Science and Engineering, Associate Professor, 大学院・工学系研究科, 助教授 (50323522)
TOYOOKA Teruhiko  The University of Tokyo, Health Service Center, Professor, 保健センター, 教授 (00146151)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥14,200,000 (Direct Cost: ¥14,200,000)
Fiscal Year 2003: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2002: ¥12,100,000 (Direct Cost: ¥12,100,000)
KeywordsBONE / CARTILAGE / BLOOD VESSEL / REGENERATION / GENE DELIVERY / 再生医療 / 複合組織再生
Research Abstract

To establish a clinically useful method to regenerate bone and cartilage, we have obtained the following results :
1.As for new scaffolds, we developed a hybrid mesh composed of PLGA and collagen. The thickness of the hybrid mesh was adjustable, and the hybrid mesh had both good strength and biocompatibility. When we seeded bovine chondrocytes into the hybrid mesh, the cells attached to it efficiently, producing rich cartilaginous matrices, and their dedifferentiation was suppressed. We conclude that the hybrid mesh has advantages over other scaffblds.
2.As for new culture systems, we developed a rotational, culture method, in which culture dishes were rotated horizontally, and spheroids were formed by clusters of cells. With this system, we were able to assess effects of differentiation and proliferation stimuli on osteoblasts and chondroeytes in a more physiologic setting. We were also able to generate osteoblast and chondrocyte spheroids on, a large scale, which we plan to seed into the scaffold to develop artificial bone and cartilage.
3.As for new methods to induce osteogenie and chondrogenic differentiation, we clarified the role of IINOS and intracellular calcium in osteoblastic differentiation. By applying this finding, we could reverse the suppression of osteoblastic differentiation by iNOS through down-regulating mRNA expression of iNOS with RNAi.
4.As for regeneration of blood vessels, we found that the bFGF was superior to VEGF in induction, and that the combination of both proved even better.
We conclude that this project has successfully established the basal technologies that will help realize regeneration of bone and cartilage by a hovel 3-D culture system based on formation of vascular network.

Report

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

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Suenaga H., Furukawa S.K., Ushida T., Takato T., Tateishi T.: "Aggregate formation of bone narrow stromal cells by rotation culture"Mat.Sci.Eng.C. (印刷中). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Koizumi T., Hikiji H., Wee Soo Shin, Takato T., Fukuda S., Abe T., Koshikiya N., Iwasawa K., Toyo-oka T.: "Cell Dentistry and growth-dependent down-regulation of both intracellular calcium responses to agonist stimuli and expression of smooth-surfaced endoplasmic reticulum in MC3T3-E1 osteoblast-like cells."J Biol Chem. 278. 6433-6439 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Abe T., Hikiji H., Shin W.S., Koshikiya N., Shima S., Nakata.J., Susamu T., Takato T., Toyo-oka T.: "Targeting of iNOS with antisense DNA plasmid reduces cytokine-induced inhibition of osteoblastic activity."Am.J.Physion Endocrinol Metab.. 285. E614-E621 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Chen G, Sato T, Ushida T, Hirochika R, Shirasaki Y, Ochiai N, Tateishi T: "The use of a novel PLGA fiber/collagen composite web as a scaffold for engineering of articular cartilage tissue with adjustable thickness"J Biomed Mater Res. 67A. 1170-1180 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Chen G, Sato T, Ushida T, Hirochika R, Tateishi T.: "Redifferentiation of dedifferentiated bovine chondrocytes when cultured in vitro in a PLGA-collagen hybrid mesh."FEBS Lett. 542. 95-99 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kondoh- K, Koyama H, Miyata T, Takato T, Hamada H, Shigematsu H.: "Conduction performance of collateral vessels induced by vascular endothelial growth factor or basic fibroblast growth factor."Cardiovasc Res. 61. 132-142 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suenaga H., Furukawa S.K., Ushida L., Takato T., Tateishi T.: "Aggregate formation of bone marrow stromal cells by rotation culture"Mat.Sci.Eng.C. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Koizumi T., Hikiji H., Wee Soo Shin, Takato T., Fukuda S., Abe T., Koshikiya N., Iwasawa K., Tovo-oka T.: "Cell Dentistry and growth-dependent down-regulation of both intracellular calciiini responses to agonist, stimuli and expression of smooth-surfaced endoplasmic reticulum in MC3T3-E1 osteoblast-like cells."J Biol Chem. 278. 6433-6439 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Abe T., Hikiji H., Shin W.S, Koshikiya N., Shima S., Nakata J., Susarni T., Takato T., Toyo-oka T.: "Targeting of iNOS with antisense DNA plasmid reduces cytoldne-induced inhibition of osteoblastlc activity."Am.J.Physion Endocrinol Metab.. 285. E614-E621 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Chen G, Sato T, Ushida T, Hirochika R, Shirasaki Y, Ochiai N, Tateishi T: "The use of a novel PLGA fiber/collagen composite web as a scaffold for engineering of articular cartilage tissue with adjustable thickness"J Biomed Mater Res. 67A. 1170-1180 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Chen G, Sato T, Ushida T, Hirochika R, Tateishi T.: "Redifferentiation of dedifferentiated bovine chondrocytes when cultured in vitro in a PLGA-collagen hybrid mesh."FEBS Lett. 542. 95-99 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kondoh K, Koyania H, Miyata T, Takato T, Hamada H, Shigematsu H.: "Conduction performance of collateral, vessels induced by vascular endothelial growth factor or basic fibroblast growth factor."Cardiovasc Res. 61. 132-142 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Suenaga H., Furukawa S.K., Ushida T., Takato T., Tateishi T.: "Aggregate formation of bone marrow stromal cells by rotation culture"Mat.Sci.Eng.C. (印刷中). (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Koizumi T., Hikiji H., Wee Soo Shin, Takato T., Fukuda S., Abe T., Koshikiya N., Iwasawa K., Toyo-oka T.: "Cell Dentistry and growth-dependent down-regulation of both intracellular calcium responses to agonist stimuli and expression of smooth-surfaced endoplasmic reticulum in MC3T3-E1 osteoblast-like cells."J Biol Chem. 278. 6433-6439 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Abe T., Hikiji H..Shin W.S., Koshikiya N., Shima S., Nakata J., Susami T., Takato T., Toyo-oka T.: "Targeting of iNOS with antisense DNA plasmid reduces cytokine-induced inhibition of osteoblastic activity."Am.J.Physion Endocrinol Metab.. 285. E614-E621 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Chen G, Sato T, Ushida T, Hirochika R, Shirasaki Y. Ochiai N, Tateishi T: "The use of a novel PLGA fiber/collagen composite web as a scaffold for engineering of articular cartilage tissue with adjustable thickness."J Biomed Mater Res. 67A. 1170-1180 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Chen G, Sato T, Ushida T, Hirochika R, Tateishi T: "Redifferentiation of dedifferentiated bovine chondrocytes when cultured in vitro in a PLGA-collagen hybrid mesh."FEBS Lett. 542. 95-99 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kondoh K, Koyama H, Miyata T, Takato T, Hamada H, Shigematsu H: "Conduction performance of collateral vessels induced by vascular endothelial growth factor or basic fibroblast growth factor."Cardiovasc Res. 61. 132-142 (2004)

    • Related Report
      2003 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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