Pandey Shashank, Dvorakova Magdalena C
Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic.
Department of Physiology, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic.
Endocr Metab Immune Disord Drug Targets. 2020;20(1):25-38. doi: 10.2174/1871530319666190626143832.
The need of today's research is to develop successful and reliable diabetic animal models for understanding the disease susceptibility and pathogenesis. Enormous success of animal models had already been acclaimed for identifying key genetic and environmental factors like Idd loci and effects of microorganisms including the gut microbiota. Furthermore, animal models had also helped in identifying many therapeutic targets and strategies for immune-intervention. In spite of a quite success, we have acknowledged that many of the discovered immunotherapies are working on animals and did not have a significant impact on human. Number of animal models were developed in the past to accelerate drug discovery pipeline. However, due to poor initial screening and assessment on inequivalent animal models, the percentage of drug candidates who succeeded during clinical trials was very low. Therefore, it is essential to bridge this gap between pre-clinical research and clinical trial by validating the existing animal models for consistency.
In this review, we have discussed and evaluated the significance of animal models on behalf of published data on PUBMED. Amongst the most popular diabetic animal models, we have selected six animal models (e.g. BioBreeding rat, "LEW IDDM rat", "Nonobese Diabetic (NOD) mouse", "STZ RAT", "LEPR Mouse" and "Zucker Diabetic Fatty (ZDF) rat" and ranked them as per their published literature on PUBMED. Moreover, the vision and brief imagination for developing an advanced and robust diabetic model of 21st century was discussed with the theme of one miceone human concept including organs-on-chips.
当今研究的需求是开发成功且可靠的糖尿病动物模型,以了解疾病易感性和发病机制。动物模型在识别关键遗传和环境因素(如Idd基因座)以及微生物(包括肠道微生物群)的影响方面已取得巨大成功。此外,动物模型还有助于识别许多免疫干预的治疗靶点和策略。尽管取得了相当大的成功,但我们也承认,许多已发现的免疫疗法在动物身上有效,但对人类却没有显著影响。过去开发了许多动物模型以加速药物研发流程。然而,由于对不等价动物模型的初始筛选和评估不佳,临床试验中成功的候选药物比例非常低。因此,通过验证现有动物模型的一致性来弥合临床前研究与临床试验之间的差距至关重要。
在本综述中,我们根据PUBMED上发表的数据讨论并评估了动物模型的重要性。在最受欢迎的糖尿病动物模型中,我们选择了六种动物模型(如BioBreeding大鼠、“LEW IDDM大鼠”、“非肥胖糖尿病(NOD)小鼠”、“链脲佐菌素大鼠”、“瘦素受体小鼠”和“Zucker糖尿病脂肪(ZDF)大鼠”),并根据它们在PUBMED上发表的文献进行排名。此外,还以一鼠一人概念(包括芯片器官)为主题,讨论了开发先进且强大的21世纪糖尿病模型的愿景和简要设想。