Project/Area Number |
14370510
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Urology
|
Research Institution | Kyoto University |
Principal Investigator |
ITO Noriyuki Kyoto University, Graduate School of Medicine, Lecturer, 医学研究科, 講師 (70343225)
|
Co-Investigator(Kenkyū-buntansha) |
TABATA Yasuhiko Kyoto University, Institute for Frontier Medical Sciences, Biomaterial, Professor, 再生医科学研究所, 教授 (50211371)
OGAWA Osamu Kyoto University, Graduate School of Medicine, Urology, Professor, 医学研究科, 教授 (90260611)
YAMAMOTO Shingo Kyoto University, Graduate School of Medicine, Urology, Lecturer, 医学研究科, 講師 (80322741)
KAMOTO Toshiyuki Kyoto University, Graduate School of Medicine, Urology, Associate Professor, 医学研究科, 助教授 (00281098)
NISHIYAMA Hiroyuki Kyoto University, Graduate School of Medicine, Urology, Lecturer, 医学研究科, 助手 (20324642)
|
Project Period (FY) |
2002 – 2004
|
Project Status |
Completed (Fiscal Year 2004)
|
Budget Amount *help |
¥13,700,000 (Direct Cost: ¥13,700,000)
Fiscal Year 2004: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2002: ¥8,500,000 (Direct Cost: ¥8,500,000)
|
Keywords | Bladder Acellular Matrix(BAM) / Collagen Type I / Growth Factor / Angiogenesis / Bladder Smooth Muscle Cell / Bone Marrow Mesenchymal Stem Cell / Basic Fibroblast Growth Factor(bFGF) / Regenerative Medicine / 膀胱再生 / 塩基性線維芽細胞増殖因子 / 細胞外マトリクス / 徐放 / 膀胱 / 尿道 |
Research Abstract |
1)Bladder regeneration by bladder acellular matrix combined with sustained release of exogenous growth factor (Reference 1). The bladder acellular matrix (BAM) functioned as release carrier of bFGF by itself. When the BAM containing bFGF was used as repair graft in a rat bladder augmentation model, angiogenesis into the matrix was promoted and graft shrinkage was significantly inhibited by incorporated bFGF in a dose dependent manner. 2)Collagenous matrices as release carriers of exogenous growth factors (Reference 2). The property of BAM for the release of various growth factors was similar to that of pure Type I collagen sponge. 3)Type I collagen can function as a reservoir of basic fibroblast growth factor (Reference 3). bFGF interacts with type I collagen solution and sponges under in vitro and in vivo physiological conditions, and is protected from the proteolytic environment by the collagen. This property could be successfully applied for treatment of severe ischemic limb. 4)Induction of smooth muscle cell-like phenotype in marrow-derived cells on bladder acellular matrix (Reference 4) In bladder repair model, bone marrow-derived cells reconstituted the smooth muscle layer on acellular graft, with native smooth muscle cells (SMC) infiltrating the graft. In vitro, growth factor milieu characteristic of SMC induced an SMC-like phenotype in marrow cells, whereas that of urothelial cells failed. In summary, we have created a novel release system from animal-derived extracellualr matrix biomaterial, and demonstrated an unrecognized role of Type I collagen for controlling the function of growth factors. Reference 3 demonstrates a clinical applicability of this principle for treating ischemic conditions. In parallel, we have investigated roles of growth factors for smooth muscle regeneration, and presented an innovative mechanism that governs the bladder regeneration in References 1 and 4.
|