Kanematsu Akihiro, Yamamoto Shingo, Noguchi Tetsuya, Ozeki Makoto, Tabata Yasuhiko, Ogawa Osamu
Department of Urology, Institute for Frontier Medical Science, Kyoto Univeristy, Japan.
J Urol. 2003 Oct;170(4 Pt 2):1633-8. doi: 10.1097/01.ju.0000084021.51099.8a.
We investigate the use of bladder acellular matrix (BAM) as a carrier of exogenous growth factor.
Basic fibroblast growth factor (bFGF) protein was loaded in a lyophilized BAM by rehydrating the matrix with the growth factor solution. In vitro and in vivo release of bFGF from BAM was traced by radiolabeled bFGF. To assess biological effect of the released bFGF, BAMs incorporating bFGF were implanted into back subcutis of mice and vascular endothelial growth factor levels in the local tissue were determined. Furthermore, bladder augmentation was performed in rats with BAM grafts containing various concentrations of bFGF. At 4 and 12 weeks the graft size at maximal cystometric capacity was evaluated, followed by histological and physiological evaluation.
Sustained release of bFGF from BAM was observed in vitro and in vivo. In vivo biological activity of bFGF in BAM as determined by vascular endothelial growth factor levels was preserved for more than 3 weeks. In the bladder augmentation model angiogenesis into the matrix was promoted and graft shrinkage was significantly inhibited by incorporated bFGF in a dose dependent manner at 4 weeks.
BAM can function as a platform for sustained release of exogenous bFGF. This delivery method of growth factor could be a useful tool for bladder reconstruction.
我们研究膀胱脱细胞基质(BAM)作为外源性生长因子载体的用途。
通过用生长因子溶液复水冻干的BAM来加载碱性成纤维细胞生长因子(bFGF)蛋白。用放射性标记的bFGF追踪bFGF在体外和体内从BAM中的释放情况。为评估释放的bFGF的生物学效应,将掺入bFGF的BAM植入小鼠背部皮下,测定局部组织中的血管内皮生长因子水平。此外,对含有不同浓度bFGF的BAM移植物进行大鼠膀胱扩大术。在4周和12周时评估最大膀胱测压容量时的移植物大小,随后进行组织学和生理学评估。
在体外和体内均观察到bFGF从BAM中持续释放。通过血管内皮生长因子水平测定,BAM中bFGF的体内生物学活性在3周以上得以保留。在膀胱扩大模型中,4周时掺入的bFGF以剂量依赖方式促进了基质内的血管生成,并显著抑制了移植物收缩。
BAM可作为外源性bFGF持续释放的平台。这种生长因子递送方法可能是膀胱重建的有用工具。