2005 Fiscal Year Final Research Report Summary
The development of brand new therapy for therapy resistant lung disease (interstitial pneumonia and emphysema)
| Project/Area Number |
16590769
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | Kurume University |
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Principal Investigator |
YUGE Kentaro Kurume University, School of medicine, Assistant professor, 医学部, 助手 (00258485)
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| Co-Investigator(Kenkyū-buntansha) |
AIZAWA Hisamichi Kurume University, School of medicine, Professor, 医学部, 教授 (90175711)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Emphysema / Interstitial Pneumonia / adenovirus / HGF / HB-EGF / TGF-β / Stem Cell Transplantation |
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| Research Abstract |
The development of brand new therapy for therapy resistant lung disease (interstitial pneumonia and emphysema)
I.The trial of the therapy of interstitial pneumonia by gene transduction of adenovirus vector with HGF, HB-EGF and the fusion of extracellular domain of TGF-β receptor II and human IgG Fc portion gene.
1.The trial of the therapy of interstitial pneumonia by gene transduction of adenovirus vector with TGF-β receptor II and human IgG Fc portion gene (Ad.CAG.TGF-β RII/IgG Fc). The TGF-β receptor II and human IgG Fc portion fusion protein which was expressed by Ad.CAG.TGF-β RII/IgG Fc infected 293 cells suppressed the effect of TGF-β. In preparative study, the therapeutic effects were seen in interstitial pneumonia model mouse by transduction of Ad.CAG.TGF-β RII/IgG Fc. It will be the effective therapy if the duration of the protein expression and the immunogenicity of adenovirus are solved.
II.The trials of emphysema by gene trunsduction of HGF, HB-EGF and mesenchymal stem cells.
The trial of the therapy of emphysema by gene transduction of adenovirus vector with human HGF gene (Ad.CAG.HGF).
The obvious improvement was seen in mouse emphysema models by Ad.CAG.HGF injected to hind limbs in contrast to that in Ad.CMV.LacZ injected mouse models. The alveolar structure was more conserved in Ad.CAG.HGF injected group than in Ad.CMV.LacZ injected group. The decrease of tunnel positive cells was seen in Ad.CAG.HGF injected group, so we thought that HGF suppresses the apoptosis of alveolar cells in emphysema as the mechanism of improvement effect of HGF. The cell growth effect and angiogenic effect were also recognized in Ad.CAG.HGF injected group compared with Ad.CMV.LacZ injected group, though statistical differences were not seen.
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