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2003 Fiscal Year Final Research Report Summary

Molecular biological analyses of cranio-maxillo-facial bone metabolism and application of the gene therapy

Research Project

Project/Area Number 14370572
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) AKIDA Sadanori  Nagasaki University Medical and dental School Hospital, Assistant Professor, 医学部・歯学部附属病院, 助手 (90315250)
FUJII Tohru  Nagasaki University, Graduate School of Biomedical Sciences, Emeritus Professor, 大学院・医歯薬学総合研究科, 名誉教授 (60136661)
Project Period (FY) 2002 – 2003
Keywordshuman mesenchymal stem cell / gene therapy / abnormal bone metabolism / ultrastructure / bone morphogenetic protein-2 / basic fibroblast growth factor / 頭蓋欠損モデル
Research Abstract

The human modesenchymal stem cells,(hMSCs) are highly proliferative and cell-cycle regulated by applications of bone morphogenetic protein-2 (BMP-2) and basic fibroblast growth factor (bFGF). The gene expressions of the cell cycles such as BrDU, PCNA (proliferating cell nuclear antigen) and PTTG (pituitary tumor transforming gene) are well demonstrated at entire, GO/G1 and G2/M phase, respectively. Ultrastrucural analyses revealed that hMSCs are differentiated upon BMP-2 administration by changing the nuclear (of euchromatin to heterochromatin) and cytoplasmic (smooth endoplasmic reticulum to granular endoplasmic reticulum) morphology. In regenerative medicine using hMSCs and the proper scaffold such as a natural gelatin, there are accelerated cranial bone regeneration together with BMP-2 and bFGF_initiations. High expression levels of alkaline phosphatase (ALP) in osteogenic medium culture, which contains dexamethasone, ascorbic acid, and beta-glycerophosphate, observed in both supernatant and cells. In 4 weeks after transplanting hMSCs and osteogenic cytokines demonstrated the significant immunohistochemical expressions of human ALP and osteocalcin as well as increased bone mass. These results may explain that hMSCs are useful in regenerative medicine in osteogenic lineage. In future, this regimen may be used in conjunction with gene therapy on hMSCs for severe abnormal bone metabolism.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Daian T, Hirano A, Fujii T, et al.: "IGF-1 Enhances TGF-B-induced Extracellular Matrix Protein Production through the p38/ATF-2 Signaling Pathway in Keloid Fibroblasts"J Invest Dermatol. 120. 956-962 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Akino K, Mineta T, Fukui M, Fujii T, Akita S.: "Bone morphogenetic protein-2 regulates proliferation of human mesencymal stem cells"Wound Repair Regen. 11. 354-360 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Akita S, Nakagawa H, Akino K, Fukui M, Fujii T: "Cellules souches pour la cicatrisation des plaies cutanees"Journal des Plaies et Cicatrisations. 8. 13-17 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Akita S, Fukui M, Nakagawa H, Fujii T, Akino K: "Cranial bone defect healing is accelerated by mesenchymal stem cell by co-administration of bone morphogenetic protein-2 and basic fibroblast growth factor"Wound Repair Regen. 12. 254-261 (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 平野明喜, 鈴木弘之: "口唇裂、口蓋裂患者の顎骨骨切り術施行におけるチーム医療 形成外科と矯正歯科の立場より"形成外科. 45:3. 223-230 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 平野明喜, 江頭通弘, 横内哲博, 藤井徹, 村上隆一: "呼吸・食物摂食障害に対する口腔底筋骨膜下剥離術"日本形成外科学会会誌. 22:10. 703-708 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Akita S, Fukui M, Fujii T, Akino K: "ETRS Proceedings of Focus Meeting : New Technologies in Wound Healing"Positif Press, Oxford(In press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Daian T, Ohtsuru A, Rogounovitch T, Ishihara H, Hirano A, Akiyama-Uchida Y, Saenko V, Fujii T, Yamashita S.: "Overexpression of insulin-like growth factor-1 (IGF-I) receptor and the invasiveness of cultured keloidfibroblasts."J invest Dermatol.. 120. 956-962 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akino K, Mineta T, Fukui M, Fujii T, Akita S.: "Bone morphogenetic protein-2 regulates proliferation of human mesenchymal stem cells."Wound Rep Reg.. 11. 354-360 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akita S, Nakagawa H, Akino K, Fukui M, Fujii T.: "Cellules souches pour la cicatrisation des plates cutanees"Journal des Plaies et Cicatrisations. 8. 13-17 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fukui M, Akita S, Akino K.: "Ectopic bone, formation facilitated by human mesenchymal stem cells and osteogenic cytokines via nutrient vessel injection in a nude rat model."Wound Rep Reg.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Akita S, Rashid MA, Ishihara H, Daian T, Dazai S, Fujii T: "Cytokine-dependent gp130 receptor subunit regulates rat modified axial-pattern epigastric flap"J invest surg. 15. 137-151 (2002)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2005-04-19  

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