BMSCs、EPCs和ATM组织工程尿道在犬体内的重塑效果和机理研究

The dog is man's most reliable friend, as well as a laboratory animal for man's medical research. Urethral defect, a common surgical disease in men and dogs, is caused by urethral injury, tumor resection or urethral calculi, or by segmental urethral necrosis due to various reasons. At present, circumferential urethral defect is merely treated with urethrostomy both in human medicine clinics and veterinary clinics, which, however, cannot avoid the complications and sequelae (such as local wet dermatitis, chronic urinary tract infections, or even hyperplasia, stenosis or occlusion at the stoma). The project is designed to initially study the self-repair capacity of dogs (as test animals) to circumferential urethral defect, then the tissue engineered construction of urethra with canine bone marrow mesenchymal stem cells (BMSCs) and endothelial progenitor cells (EPCs) and ovine urinary acellular tissue matrices (ATM) scaffold, and the repair effects of canine long-section circumferential urethral defect by tissue engineered urethra, in order to look for new avenues for veterinary clinical treatment to canine long-section circumferential defects. In the project, the proliferation and differentiation rules of the seed cells will be researched by fluorescent labeling in order to figure out the preliminary mechanism of the reconstruction and modeling of the tissue engineered urethra in dogs and provide large animal test data for human medical research.

犬是人类最忠实的朋友，也是医学研究不可或缺的试验动物。尿道缺损是人和犬均发的一种常见外科病，由尿道损伤、肿瘤切除、结石、或各种原因所导致的尿道节段性坏死所引起。目前，不论是人医临床还是兽医临床对管状尿道缺损病例只能采用尿道造口术进行治疗，难以避免手术并发症和后遗症(局部尿湿性皮炎，慢性尿道感染，造口处增生、狭窄或闭塞)。本项目拟用犬作试验动物，从研究犬对管状尿道缺损的自身修复能力入手，系统研究采用同种异体骨髓间充质干细胞(BMSCs)、内皮祖细胞(EPCs)和异种尿道脱细胞基质(ATM)支架构建组织工程尿道，以及组织工程尿道对管状尿道缺损的修复效果，为兽医临床彻底治疗犬的长段管状尿道缺损开辟新途径。进一步对种子细胞进行荧光标记，示踪其增殖和分化规律，初步弄清它们参与尿道重建和塑型的机理，为人类医学研究提供大型动物试验资料。

组织工程尿道是修复犬尿道缺损的理想方法。本课题在完成 “膀胱-包皮吻合术”为骨盆部尿道缺损犬重建尿路研究和犬对管状尿道缺损自身修复能力研究的基础上，采用同种异体骨髓间充质干细胞(BMSCs)、内皮祖细胞(EPCs)和羊膜脱细胞基质支架构建组织工程尿道，采用组织工程尿道修复犬3cm长管状尿道缺损，取得了良好的修复效果，并且进行了组织工程尿道在体内塑型过程中种子细胞的分化归宿（塑型机理）研究，为兽医临床彻底治疗犬的长段管状尿道缺损开辟新途径。此外，在本课题的延伸研究中，将BMSCs体外诱导分化成胰岛样细胞团，并将胰岛样细胞团标记后移植到糖尿病模型动物体内，使其血糖趋于正常，为糖尿病治疗开辟了新途径。项目资助发表论文6篇，待发表论文4篇；培养硕士生8名，其中6名已经取得硕士学位，2名在读。项目投入经费85万元，支出70.6928万元，各项支出基本与预算相符。剩余经费14.3072万元，计划用于本项目后续研究支出。