Development of a theraputic model for osteoporosis with stem cells combination with OSF1 gene.
| Project/Area Number |
16591507
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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 |
Orthopaedic surgery
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
TSUJIMURA Atsushi Koto Prefectural University of Medicine, Graduate school of medical science, research associate, 医学研究科, 助手 (50236890)
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| Co-Investigator(Kenkyū-buntansha) |
HASHIMOTO Tamotsu (GOTOH Tamotsu) Koto Prefectural University of Medicine, Graduate school of medical science, assistant professor, 医学研究科, 助教授 (00237942)
KUBO Toshikazu Koto Prefectural University of Medicine, Graduate school of medical science, professor, 医学研究科, 教授 (20178031)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2004: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | Osteoporosis / Stem cells / gene therapy / 細胞治療 |
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| Research Abstract |
Osteoporosos is caused by many factors such as diet, exercise, hormonal unbalance and getetic background and in the state of bone loss by the exess bone-resorption than the bone formation. Some medicatons, which prevent bone resorption, bisphosphonate for example, are used for osteoporosis. We proposed a novel theraputic method, a combination of gene therapy and stem cell plantation. In this method, mesentymal stem cells (MSC) integrated with osteoblast stimulating factor 1(OSF1) gene was transplanted into a osteoporosis model in anticipation of active bone formation by recrueted stem cells to right place for bone foamation and differentiated into osteoblasts.
For preparation of OSF1 integrated MSC, transgenic mice carrying human OSF1 and EGFP gene as transplantation marker were constructed and therir bone structure was analyzed by micro-CT. The trabecular number was increased in tibia of OSF1 transgenic mouse compared to control GFP expressing mouse. Bone formation stimulation was also
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observed in primery cultured osteoblasts derived from new-born tg mouse calvaria. Tg derived MSC was cultured in osteo inductive medium then ALP activity and Ca deposition was mesured after 3 week incubation. Both osteogenesis markers were stimulated in OSF1 expressing MSC and more enhancements was observed in the presence of BMP2. Exceptionally in the MSC, which have extremely high level OSF1 expression, osteogenesis was inhibited in the presence or absence of BMP2. It was speculated that the optimal OSF1 expression level exist and it is necessary to optimize the OSF1 expression level for in vivo experiments. Moreover, drastical inhibition in osteogenesis of MSC was observed in omiting the pre-culture in amplification medium prior to the osteo induction. This indicates that accumulation of some factors during the pre-culture period is required for effective osteogenesis and that identification of these factors lead to more effective transplantation and successful osteoporosis therapy. Less
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Report
(3 results)
Research Products
(3 results)
