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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 16591795
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

AKITA Sadanori  Nagasaki University, Hospital of Medicine and Dentistry, Assistant Professor, 医学部・歯学部附属病院, 助手 (90315250)

Co-Investigator(Kenkyū-buntansha) 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)
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)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2005: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2004: ¥2,700,000 (Direct Cost: ¥2,700,000)
Keywordshuman mesenchymal stem cells / differentiation lineage / trans-differentiation / proliferation and differentiation / cellular interaction / fibroproliferative disease / clinical application / 創傷治癒 / サイトカイン / 骨髄間葉系幹細胞 / 水分量 / 臨床評価 / 分子機構 / 瘢痕の質 / 上皮転換 / 骨髄由来幹細胞 / 間葉系マーカー / ヌードラット
Research Abstract

Extensive burns and massive tissue loss lead to life-threatening sequelae. Autogenic tissues and cells are not sufficient enoght for wound coverage. These situations should be treated emergently and well-prepared. The human mesenchymal stem cells (hMSC) are self renewal and proliferative and differentiated into ectodermal and endodermal lineage of neuronal tissue and repair, endothelial differentiation or liver regeneration as well as mesenchymal lineage such as bone, cartilage, tendon, fat, or muscle. The artificial skin substitute of porcine tendon collagen-derived bilayer product, Pelnac【○!R】, is used for coverage for wound and sustaining carrier of grafted hMSC and stimuli of hMSC such as basic Fibroblast Growth Factor, bFGF. 1.5×1.5 cm^2 nude rat back defect was covered with 5×10^2hMSC and bFGF successfully significantly closed the wound by day 7. The histology of the regenerated tissue demonstrated the human-specific epithelial markers as well as Western blot analysis of the tiss … More ue demonstrated the human-specific pan-cytokeratin expression. The chemotactic migration assay using the 8 μm pore-sized diaphragmatic membrane demonstrated the highest interaction between hMSC and epidermal keratinocyte in comparison with other cell types such as dermal fibroblast or endothelial cell. Clinically, severe local infected wound caused by necrotizing fasciitis successfully are covered with temporal use of artificial skin substitute after extensive debridement. In buns, bFGF application with split-skin grafting right after debridement improved the scar quality on clinical score and hardness measured by durometer. In pediatric burns, early administration of bFGF in II degree burns demonstrated the subsequent inhibition of hypertrophic scars and better corneal layer function. On the other hand, cysteinyl leukotriene receptor antagosist on hMSC depicted fibroblast-like morphology and production of extra-cellular matrix. This may be implicated in fibroproloferative diseases as well. Less

Report

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

    (36 results)

All 2005 2004 Other

All Journal Article (31 results) Book (5 results)

  • [Journal Article] Human mesenchymal stem cells successfully improve skin-substitute wound healing.2005

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

      Br J Dermatol 153

      Pages: 29-36

    • 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 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(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] A basic fibroblast growth factor improved the quality of skin grafting in burn patients.2005

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

      Burns 31

      Pages: 855-858

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] A novel molecular marker of pituitary tumor-transforming gene involved in rat liver regeneration.2005

    • Author(s)
      Akino K, Akita S, Mizuguchi T, Takumi I, Yu R, Wang X-Y, Rozga J, Demetriou AA, Melmed S, Ohtsuru A, Yamashita S.
    • Journal Title

      J Surg ReS 129

      Pages: 142-146

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Analysis of pediatric burns in Nagasaki University from 1983 to 2002.2005

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

      Burns 31

      Pages: 1041-1044

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Human mesenchymal stem cells successfully improve skin-substitute wound healing.2005

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

      Br J Dermatol. 153

      Pages: 29-36

    • 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 human mesenchymal 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] A basic fibroblast growth factor improved the quality of skin grafting in burn patients.2005

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

      Burns. 31

      Pages: 855-858

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A novel molecular marker of pituitary tumor-transforming gene involved in rat liver regeneration.2005

    • Author(s)
      Akino K, Akita S, Mizuguchi T, Takumi I, Yu R, Wang X-Y, Rozga J, Demetriou AA, Melmed S, Ohtsuru A, Yamashita S.
    • Journal Title

      J Surg Res. 129

      Pages: 142-146

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Analysis of pediatric burns in Nagasaki University from 1983 to 2002.2005

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

      Burns. 31

      Pages: 1041-1044

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [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 153

      Pages: 29-36

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Lower extremity reconstruction after necrotizing fasciitis and necrotic skin lesions using a porcine-derived skin substitute2005

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

      Br J Plast Surg (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] The quality of pediatric burn scars is improved by early administration of basic fibroblast growth factor2005

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

      J Burn Care Research (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 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] Leukemia inhibitory factor-transfected embryonic fibroblasts and vascular endothelial growth factor successfully improve the skin substitute wound healing by increasing angiogenesis and matrix production.2004

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

      J Dermatol Sci 36

      Pages: 11-23

    • NAID

      10016185020

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Leukemia inhibitory factor-transfected embryonic fibroblasts and vascular endothelial growth factor successfully improve the skin substitute wound healing by increasing angiogenesis and matrix production.2004

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

      J Dermatol Sci. 36

      Pages: 11-23

    • NAID

      10016185020

    • 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] Lower extremity reconstruction after necrotizing fasciitis and necrotic skin lesions using a porcine-derived skin substitute.

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

      Br J Plast Surg (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The quality of pediatric burn scars 15 improved by early administration of basic fibroblast growth factor.

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

      J Burn Care Rehabil (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Polyurethane dressing is beneficial for split-thickness skin-graft donor wound healing.

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

      Burns (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Elevated circulating leukemia inhibitory factor levels in burn patients : marker of mortality.

    • Author(s)
      Akiat S, Akino K, Ren SG, Melmed S, Imaizumi T, Hirano A.
    • Journal Title

      J Burn Care Rehabil (in press)

    • 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] Lower extremity reconstruction after necrotizing fasciitis and necrotic skin lesions using a porcine-derived skin substitute.

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

      Br J Plast 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] The quality of pediatric burn scars is improved by early administration of basic fibroblast growth factor.

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

      J Burn Care Rehabil (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] Polyurethane dressing is beneficial for split-thickness skin-graft donor wound healing.

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

      Burns (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] Elevated circulating leukemia inhibitory factor levels in burn patients : marker of mortality.

    • Author(s)
      Akita S, Akino K, Ren SG, Melmed S, Imaizumi T, Hirano A.
    • Journal Title

      J Burn Care Rehabil (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 Annual Research 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.)ETRS Bulletin Oxford2005

    • Author(s)
      Akita S, Fukui M, Fujii T, Akino K.
    • Publisher
      Positif Press.
    • 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
    • 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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