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Reconstruction of the urinary tract with biological scaffold combined with sustained release of growth factor.

生物支架联合缓释生长因子重建泌尿道。

基本信息

批准号：
14370510
负责人：
ITO Noriyuki
金额：
$ 8.77万
依托单位：
Kyoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370510/
关键词：
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

项目摘要

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.

1)膀胱脱细胞基质与外源性生长因子缓释相结合的膀胱再生(参考文献1)，膀胱脱细胞基质(BAM)本身作为bFGF的释放载体。将含碱性成纤维细胞生长因子的BAM用作大鼠膀胱增大模型的修复移植物时，以剂量依赖的方式掺入碱性成纤维细胞生长因子促进基质中的血管生成，显著抑制移植物的收缩。2)胶原基质作为外源性生长因子的释放载体(参考文献2)，BAM释放各种生长因子的特性与纯的I型胶原海绵相似。3)I型胶原可以作为碱性成纤维细胞生长因子的储存库(参考文献3)。在体外和体内的生理条件下，bFGF与I型胶原溶液和海绵相互作用，并受到胶原蛋白的保护。4)在膀胱脱细胞基质上诱导骨髓来源的细胞表型(参考文献4)在膀胱修复模型中，骨髓来源的细胞在无细胞移植物上重建平滑肌层，天然的平滑肌细胞(SMC)渗入移植物中。在体外，SMC特有的生长因子环境诱导骨髓细胞SMC样表型，而尿路上皮细胞SMC样表型失败。综上所述，我们从动物来源的细胞外基质生物材料中创建了一种新的释放系统，并证明了I型胶原在控制生长因子功能方面的未知作用。参考文献3展示了这一原则在治疗缺血性疾病方面的临床适用性。同时，我们研究了生长因子在平滑肌再生中的作用，并在文献1和4中提出了一种管理膀胱再生的创新机制。