2003 Fiscal Year Final Research Report Summary
Molecular biological analyses of cranio-maxillo-facial bone metabolism and application of the gene therapy
| Project/Area Number |
14370572
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Plastic surgery
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| Research Institution | Nagasaki University |
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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)
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| 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)
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| Project Period (FY) |
2002 – 2003
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| Keywords | human mesenchymal stem cell / gene therapy / abnormal bone metabolism / ultrastructure / bone morphogenetic protein-2 / basic fibroblast growth factor / 頭蓋欠損モデル |
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| 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.
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