Tissue Engineering in Animal Models for Urinary Diversion: A Systematic Review

Tissue engineering and regenerative medicine (TERM) approaches may provide alternatives for gastrointestinal tissue in urinary diversion. To continue to clinically translatable studies, TERM alternatives need to be evaluated in (large) controlled and standardized animal studies. Here, we investigated all evidence for the efficacy of tissue engineered constructs in animal models for urinary diversion. Studies investigating this subject were identified through a systematic search of three different databases (PubMed, Embase and Web of Science). From each study, animal characteristics, study characteristics and experimental outcomes for meta-analyses were tabulated. Furthermore, the reporting of items vital for study replication was assessed. The retrieved studies (8 in total) showed extreme heterogeneity in study design, including animal models, biomaterials and type of urinary diversion. All studies were feasibility studies, indicating the novelty of this field. None of the studies included appropriate control groups, i.e. a comparison with the classical treatment using GI tissue. The meta-analysis showed a trend towards successful experimentation in larger animals although no specific animal species could be identified as the most suitable model. Larger animals appear to allow a better translation to the human situation, with respect to anatomy and surgical approaches. It was unclear whether the use of cells benefits the formation of a neo urinary conduit. The reporting of the methodology and data according to standardized guidelines was insufficient and should be improved to increase the value of such publications. In conclusion, animal models in the field of TERM for urinary diversion have probably been chosen for reasons other than their predictive value. Controlled and comparative long term animal studies, with adequate methodological reporting are needed to proceed to clinical translatable studies. This will aid in good quality research with the reduction in the use of animals and an increase in empirical evidence of biomedical research.组织工程与再生医学（Tissue Engineering and Regenerative Medicine, TERM）策略或可为尿流改道手术中的胃肠道组织提供替代解决方案。为推进可临床转化的相关研究，需在（大型）对照标准化动物实验中对TERM替代方案进行评估。本研究针对尿流改道动物模型中组织工程构建物的疗效相关所有证据展开调研。通过对PubMed、Embase及Web of Science三个数据库进行系统性检索，筛选出相关主题的研究。从每项纳入研究中，提取用于荟萃分析的动物特征、研究特征及实验结局数据并整理成表。此外，本研究还对研究可重复性所需的关键条目报告情况进行了评估。最终纳入的8项研究显示，其研究设计存在显著异质性，涵盖动物模型、生物材料及尿流改道类型等多个维度。所有纳入研究均为可行性研究，反映出该领域尚处于探索初期。所有研究均未设置恰当的对照组，即未与采用胃肠道组织的经典治疗方案进行对比。荟萃分析结果显示，大型动物实验呈现出更高的成功率趋势，但尚未能确定某一特定动物物种为最适配的模型。就解剖结构与手术入路而言，大型动物模型似乎更利于向临床场景转化。目前尚无法明确细胞的使用是否有助于新尿路导管的形成。现有研究未按照标准化指南对方法学与数据进行充分报告，该问题亟待改善以提升此类研究的学术价值。综上，尿流改道领域TERM相关研究所选用的动物模型，其选型依据或并非基于其预测价值。为推进可临床转化的研究，亟需开展方法学报告充分的对照、比较性长期动物实验。此举将助力高质量研究开展，减少动物使用量并提升生物医学研究的实证证据水平。