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Bone formation and optimal bone regeneration by using adult stem cells and endothelial progenitor cells and analysis of the molecular mechanism

Research Project

Project/Area Number 16390511
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Plastic surgery
Research InstitutionNagasaki University

Principal Investigator

HIRANO Akiyoshi  Nagasaki University, Graduate School of Biomedical Sciences, professor, 大学院・医歯薬学総合研究科, 教授 (90208835)

Co-Investigator(Kenkyū-buntansha) NAGAYAMA Yuji  Nagasaki University, Graduate School of Biomedical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (30274632)
AKITA Sadanori  Nagasaki University, Hospital of Medicine and Dentistry, Assistant Professor, 医学部・歯学部附属病院, 助手 (90315250)
TANAKA Katsumi  Nagasaki University, Graduate School of Biomedical Sciences, Associate Professor, 大学院・医歯薬学総合研究科, 助教授 (70244069)
AKINO Kozo  Nagasaki University, Graduate School of Biomedical Sciences, Assistant Professor, 大学院・医歯薬学総合研究科, 講師 (60284668)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 2005: ¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 2004: ¥9,700,000 (Direct Cost: ¥9,700,000)
Keywordshuman mesenchymal stem cells / osteogenic cytokines / angiogenesis / improvement of blood flow / bone transcription factor / clinical application / 異所性骨 / 骨髄由来間葉系幹細胞 / 血管柄付結合織膜弁 / 移植床血行 / 骨マーカー / 転写因子 / アルカリフォスファターゼ / オステオカルシン
Research Abstract

Human mesenchymal stem cells (hMSC) and osteogenic cytokines (Bone Morphogenetic Protein-2, BMP-2 and basic Fibroblast Growth Factor, bFGF) form and regenerate in cranial defect and in ectopic vascularized flao with a gelatin carrier as a scaffold. Regenerated bone is regulated by "mesenchymal" lineage by transcription factor in four weeks after transplantation. The bFGF enhances angiogenesis and flap blood flow as well as increases hMSC proliferation. The Green Fluorescent Protein (GFP)-transfected hMSC demonstrated transcription factor, PEB2a, expression by day 7 along with GFP-positive cells and mature bone cell marker, osteocalcin, by day 14 diffusely along with GFP-positive cells. This explains the grafted hMSCs differentiated into bone. The cells, materials, and chemical factors are all either clinically approved or eligible in the near future in Japan since at least all are approved in USA and European nations. This may be leading to mesenchymal stem cell bone regeneration in the clinical application. More data with non-human primates may be required for orthotopic and ectopic bone regeneration experiments.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (34 results)

All 2006 2005 2004 Other

All Journal Article (28 results) Book (6 results)

  • [Journal Article] PX9 and TGFB3 are linkedto susceptiblility to nonsyndromic cleft lip with or without cleft palate in the Japanese : Population-based and family-based candidate gene analyses.2006

    • Author(s)
      Ichikawa E, Watanabe A, Nakano Y, Akita S, Hirano A, Kinoshita A, Kondo S, Kishino T, Uchiyama T, Niikawa N, Yoshiura KI.
    • Journal Title

      J Hum Genet 51(epub)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Ectopic bone formation facilitated by human mesenchymal stem cells and osteogenic cytokines vita nutrient vessel injection in a nude rat model.2005

    • Author(s)
      Fukui M, Akita S, Akino K
    • Journal Title

      Woud Repair Regen 13

      Pages: 332-340

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Early cellular changes of human mesenchymal stem cells and their interacion with other cells.2005

    • Author(s)
      Akino K, Mineda T, Akita S
    • Journal Title

      Woud Repair Regen 13

      Pages: 433-440

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Surgical modifications for microform cleft lip repairs.2005

    • Author(s)
      Akita S, Hirano A
    • Journal Title

      J Cranilfact Surg 16

      Pages: 1106-1110

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Ectopic bone formation facilitated by human mesenchymal stem cells and osteogenic cytokines via nutrient vessel injection in a nude rat model.2005

    • Author(s)
      Fukui M, Akita S, Akino K.
    • Journal Title

      Wound Repair Regen. 13

      Pages: 332-340

    • NAID

      10019346306

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Early cellular changes of humanmesenchymal stem cells and their interaction with other cells.2005

    • Author(s)
      Akino K, Mineda T, Akita S.
    • Journal Title

      Wound Repair Regen. 13

      Pages: 433-440

    • NAID

      10018026912

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Surgical modifications for microform clef lip repairs.2005

    • Author(s)
      Akita S, Hirano A.
    • Journal Title

      J Craniofac Surg. 16

      Pages: 1106-1110

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Microsurgical dermal-fat transfer for progressive humifacial atroohy.2005

    • Author(s)
      Yano H, Tanaka K, Murakami R, Kaii S, Hirano A.
    • Journal Title

      J Reconstr Microsurg 21

      Pages: 15-19

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Surgical modifications for microform cleft lip repairs2005

    • Author(s)
      Akita S, Hirano A.
    • Journal Title

      J Craniofac Surg 16

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Sleep disturbances detected by a sleep apnea monitor in craniofacial surgical patients.2005

    • Author(s)
      Akita S, Anraku K, Tanaka K, Yano H, Hirano A.
    • Journal Title

      J Craniofac Surg (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Usefulness of simultaneous premaxilary osteotomy and bone grafting in the bilateral clefts.2005

    • Author(s)
      Akita S, Hirano A.
    • Journal Title

      J Craniofac Surg (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A mutation in RYK is a genetic factor for nonsyndromic cleft lip and palate2005

    • Author(s)
      Watanabe A, Akita S, Hirano A, et al.
    • Journal Title

      Cleft Palate Craniofac J (in press)

    • NAID

      10020437393

    • Related Report
      2005 Annual Research Report
  • [Journal Article] PAX9 abd TGFB3 are linked to susceptibility to nonsyndromic cleft lip with or without cleft palate in the Japanese : Population-based and family-based2005

    • Author(s)
      Ichikawa E, Akita S, Hirano A, et al.
    • Journal Title

      J Hum Genet (epub)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A mutation in RYK is a genetic factor for nonsyndromic cleft lip and palate2005

    • Author(s)
      Watanabe K, Akita S, Niikawa N, et al.
    • Journal Title

      Cleft Palate Craniofac J (in press)

    • NAID

      10029088703

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Ectopic bone formation facilitated by human mesenchymal stem cells and osteogenic cytokines via nutrient vessel injection in a nude rat model2005

    • Author(s)
      Fukui M, Akita S, Kino K
    • Journal Title

      Wound Repair Regen (in press)

    • NAID

      10019346306

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Human mesenchymal stem cells successfully improve skin substitute wound healing2005

    • Author(s)
      Nakagawa H, Akita S, Fukui M, Fujii T, Akino K
    • Journal Title

      Br J Dermatol (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Early cellular changes of human mesenchymal stem cells and their interaction with other cells2005

    • Author(s)
      Akino K, Mineda T, Akita S
    • Journal Title

      Wound Repair Regen (in press)

    • NAID

      10018026912

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Cranial bone dfect healing is accelerated by mesenchymal stem cells induced by coadministration of bone morphogenetic protein-2 and basic fibroblast growth factor2004

    • Author(s)
      Akita S, Fukui M, Nakagawa H, Fuji T, Akino K
    • Journal Title

      Wound Repair Regen 12

      Pages: 252-259

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Cranial bone defect healing is accelerated by mesenchymal stem cells induced by coadministration of bone morphogenetic protein-2 and basic fibroblast growth factor.2004

    • Author(s)
      Akita S, Fukui M, Nakagawa H, Fujii T, Akino K.
    • Journal Title

      Wound Repair Regen. 12

      Pages: 252-259

    • NAID

      10020398057

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Leukemia inhibitory factor-transfected embryonic fibroblasts and vascular endothelial growth factor successfully improve skin substitute wound healing2004

    • Author(s)
      Akita S, Daian T, Ishihara H, Fujii T, Akino K
    • Journal Title

      J Dermatol Sci 36

      Pages: 11-23

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Cranial bone defect healing is accelerated by mesenchymal stem cells induced by coadministration of bone morphogenetic protein-2 and basic fibroblast2004

    • Author(s)
      Akita S, Fukui M, Nakagawa H, Fujii T, Akino K
    • Journal Title

      Wound Repair Regen 12

      Pages: 252-259

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A mutation in RYK is a genetic factor for nonsyndromic cleftlip and palate.

    • Author(s)
      Watanabe A, Akita S, Tin NTD, Natsue N, Nakano Y, Niikawa N, Uchiyama T, Yoshiura K
    • Journal Title

      Cleft Palate Craniofac J (in press)

    • NAID

      10029088703

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Usefulness of simultaneous premaxillary osteotomy and bone grafting in the bilateral clefts.

    • Author(s)
      Akita S, Hirano A
    • Journal Title

      J Cranilfact Surg (in press)

    • NAID

      10019608012

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Attenuation of cysteinyl leukotrienes induces human mesenchymal stem cells differentiation.

    • Author(s)
      Akino K, Mineda T, Mori N, Hirano A, Imaizumi T, Akita S
    • Journal Title

      Wound Repair Regen (in press)

    • NAID

      10018197284

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A mutation in RYK is a genetic factor for nonsyndromic cleft lip and palate.

    • Author(s)
      Watanabe A, Akita S, Tin NTD, Natsume N, Nakano Y, Niikawa N, Uchiyama T, Yoshiura K.
    • Journal Title

      Cleft Palate Craniofac J, (in press)

    • NAID

      10029088703

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] sefulness of simultaneous premaxillary osteotomy and bone grafting in the bilateral clefts.

    • Author(s)
      Akita S, Hirano A.
    • Journal Title

      J Craniofac Surg, (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] PAX9 and TGFB3 are linked to susceptiblility to nonsyndromic cleft lip with or without cleft palate in the Japanese : Population-based and family-based candidate gene analyses.

    • Author(s)
      Ichikawa E, Watanabe A, Nakano Y, Akita S, Hirano A, Kinoshita A, Kondo S, Kishino T, Uchiyama T, Niikawa N, Yoshiura KI.
    • Journal Title

      J Hum Genet. 51(epub, in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Attenuation of cysteinyl leukotrienes induces human mesenchymal stem cells differentiation.

    • Author(s)
      Akino K, Mineda T, Mori N, Hirano A, Imaizumi T, Akita S.
    • Journal Title

      Wound Repair Regen, (in press)

    • NAID

      10018197284

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] The status of new technology in tissue repair at the beginning of the 21^st century.2005

    • Author(s)
      Akita S, Fukui M, Fujii T, Akino K.
    • Total Pages
      79
    • Publisher
      Cherry G,Ed.,ETRS Bulletin Oxford,Positif Press
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] The status of new technology in tissue repair at the beginning of the 21^<st> century.(Cherry G, Ed.)2005

    • Author(s)
      Akita S, Fukui M, Fujii T, Akino K.
    • Publisher
      ETRS Bulletin Oxford, Positif Press.
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] The status of new technology in tissue repair at the beginning of the 21^<st>` century.2005

    • Author(s)
      Akita S, Fukui M, Fujii T, Akino K.
    • Total Pages
      79
    • Publisher
      Cherry G, Ed., ETRS Bulletin Oxford, Positif Press
    • Related Report
      2005 Annual Research Report
  • [Book] 創傷治癒過程における感染コントロール「TIMEの視点による褥瘡ケア : 創床環境調整理論に基くアプローチ2004

    • Author(s)
      秋田定伯(大浦武彦, 田中マキコ監修)
    • Total Pages
      201
    • Publisher
      学習研究社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] Infection control in wound bed preparation. (Pressure Ulcer wound care from TIME viewpoint.)(Ohura T, Tanaka M Eds.)2004

    • Author(s)
      Akita S
    • Total Pages
      79
    • Publisher
      Gakken Co, Ltd, Tokyo
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 創傷治癒課程における感染コントロール「TIMEの視点による褥瘡ケア:創床環境調整理論に基づくアプローチ」(大浦武彦, 田中マキコ監修)2004

    • Author(s)
      秋田定伯
    • Total Pages
      201
    • Publisher
      学習研究社
    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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