| Project/Area Number |
14370461
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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 |
Orthopaedic surgery
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| Research Institution | Nagoya University |
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Principal Investigator |
ISHIGURO Naoki Nagoya University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (20212871)
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| Co-Investigator(Kenkyū-buntansha) |
KITAKOJI Takahiko Nagoya University, University Hospital, Professor, 医学部附属病院, 講師 (10303637)
KITOH Hiroshi Nagoya University, Graduate School of Medicine, Research Associate, 大学院・医学系研究科, 助手 (40291174)
KOJIMA Toshihisa Nagoya University, University Hospital, Associate, 医学部附属病院, 助手 (70378032)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥10,500,000 (Direct Cost: ¥10,500,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2003: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2002: ¥6,200,000 (Direct Cost: ¥6,200,000)
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| Keywords | distraction osteogenesis / tissue engineering / bone regeneration / osteoblast / mesenchymal stem cells / clinical application / 組識工学 |
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| Research Abstract |
Distraction osteogenesis has been successfully used for limb lengthening in patients with limb length discrepancy, severe short stature due to skeletal dysplasias. Although this treatment method is biological and has many advantages for these pathological conditions, the periods of external fixation and bone maturation is long which results in higher rates of complications such as pin track infection, joint contractures, pin loosening, delayed consolidations and fractures. The distraction osteogenesis is considered as bone regeneration models in human. So we developed rat models, and to investigate the possibility of accelerating bone formation of the distracted callus with usage of combination of cells and suitable scaffold. Bone marrow contains a population of multipotent mesenchymal stem cells(MSCs) that can be directed towards the osteogenic lineage in vitro if cultured in the presence of dexamethasone, β-glycerophosphate and ascorbic acid. Using the rat limb lengthening model, we
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revealed that transplantation of marrow derived osteoblast-like cells with collagen gel into the distracted callus promoted new bone formation and shortened the consolidation period. Also the hrFGF-2 and hrBMP-2 could stimulate the matrix synthesis and proliferation of this osteoblast-like cells derived from MSCs. The osteogenic potential of rat MSCs were reduced with passaging. In the P3 cells, osteogenic potential was severely suppressed. After acquiring these insights, we planed the clinical application of osteoblast-like cell transplantation. We started the clinical research of limb lengthening with osteoblast-like cells and plate rich plasma gels for achondroplasia and hypochondoroplasia patients under the supervision of institutional reviewer boards in Nagoya university hospital. Although the results were preliminary, transplantation of osteoblast-like cells and PRP could shorten the treatment period by acceleration of bone regeneration during distraction osteogenesis. It was clearly demantrated that eatablishiment of the culture conditions permitting the rapid expansion of MSCs is required for improvement of clinical results. Less
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