| Project/Area Number |
15390421
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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 |
Thoracic surgery
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| Research Institution | KYOTO PREFECTURAL UNIVERSITY OF MEDICINE |
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Principal Investigator |
KANDA Keiichi Kyoto Prefectural University of Medicine, Cardiovascular Surgery, Lecturer, 医学研究科, 講師 (60295649)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAYAMA Yasuhide National Cardiovascular Center Research Institute, Department of Bioengineering, Director, 生体工学部, 室長 (50250262)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥14,700,000 (Direct Cost: ¥14,700,000)
Fiscal Year 2005: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2004: ¥4,300,000 (Direct Cost: ¥4,300,000)
Fiscal Year 2003: ¥6,100,000 (Direct Cost: ¥6,100,000)
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| Keywords | Embryonic Stem Cells / Hybrid Vascular Prostheses / Mouse / Autologous Connective Tissue Tube / Mechanical Stress / マウスヌードラット / 小口径人工血管 / 再生医療 / 血管接合具 / ポリウレタン / Homodynamic Stress / マウス、ヌードラット / Hemodynamic Stress |
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| Research Abstract |
Embryonic stem cells (ES cells) are expected as alternative cell resources for autologous cell-incorporated hybrid artificial organs. However, there have been very little information about ES cell behaviors in vivo. Vascular wall cells in vivo are continuously exposed to biomechanical stimulations, such as hydrodynamic sheer stress, periodical stretching and pulsatile pressure. Therefore it is very important to know the behaviors of ES cells under such conditions when application of the cells to circulatory systems is considered.
To investigate the behavior of the ES cells under hemodynamic conditions in vivo, we developed the systematic animal experimental model of ES cell-incorporated hybrid vascular prostheses in this study.
ES cells derived from a fetal mouse were randomly differentiated on the Type IV collagen-coated culture plates in vitro to induce Flk-1+ cells. Next, the cells before and after cell sorting were seeded on the luminal surface of polyurethane vascular prostheses wit
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h a diameter of 1.5mm. After incubation with VEGF for predetermined days, the grafts were implanted to the aortas of nude rats for up to 7 days with the use of specially designed connecting devices. Implanted grafts were examined morphologically and immunologically.
After implantation, incorporated ES cells retained on the surface of the grafts under the exposure to pulsatile blood flow. Since ES cells were raveled with Lac-Z gene, it was possible to determine that the observed cells were derived from incorporated ES cells. Observed cells were polygonal shaped and did not yet exhibit the typical aspects of the vascular wall cells in this series (=<7 days). However, some of the incorporated ES cells, exhibited PECAM-1, which indicated that further in vivo differentiation of the ES cells was induced under bio-mechanical and bio-chemical stimulations.
This ES cells-incorporated hybrid vascular prosthesis is the first model for investigation of the behavior of ES cells under hemodynamic conditions in vivo, and might provide important information for clinical application of ES cell-incorporated cardiovascular artificial organs. Less
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