Veliz Diosangeles Soto, Lin Kai-Lan, Sahlgren Cecilia
Faculty of Science and Engineering, Cell Biology, Åbo Akademi University, Turku, Finland.
InFLAMES Research Flagship Center, Åbo Akademi University, Turku, Finland.
Smart Med. 2023 Feb 26;2(1):e20220030. doi: 10.1002/SMMD.20220030. Epub 2023 Feb 24.
Current biomedical models fail to replicate the complexity of human biology. Consequently, almost 90% of drug candidates fail during clinical trials after decades of research and billions of investments in drug development. Despite their physiological similarities, animal models often misrepresent human responses, and instead, trigger ethical and societal debates regarding their use. The overall aim across regulatory entities worldwide is to replace, reduce, and refine the use of animal experimentation, a concept known as the Three Rs principle. In response, researchers develop experimental alternatives to improve the biological relevance of in vitro models through interdisciplinary approaches. This article highlights the emerging organ-on-a-chip technologies, also known as microphysiological systems, with a focus on models of the vasculature. The cardiovascular system transports all necessary substances, including drugs, throughout the body while in charge of thermal regulation and communication between other organ systems. In addition, we discuss the benefits, limitations, and challenges in the widespread use of new biomedical models. Coupled with patient-derived induced pluripotent stem cells, organ-on-a-chip technologies are the future of drug discovery, development, and personalized medicine.
当前的生物医学模型无法复制人类生物学的复杂性。因此,经过数十年的研究以及在药物研发上的数十亿美元投资,近90%的候选药物在临床试验中失败。尽管动物模型与人类在生理上有相似之处,但它们常常不能准确反映人类的反应,反而引发了关于其使用的伦理和社会辩论。全球各监管机构的总体目标是取代、减少和优化动物实验的使用,这一理念被称为“3R原则”。作为回应,研究人员通过跨学科方法开发实验替代方案,以提高体外模型的生物学相关性。本文重点介绍了新兴的芯片器官技术,也称为微生理系统,特别关注血管模型。心血管系统在负责体温调节以及与其他器官系统通信的同时,将包括药物在内的所有必需物质输送到全身。此外,我们还讨论了新生物医学模型广泛应用中的益处、局限性和挑战。与患者来源的诱导多能干细胞相结合,芯片器官技术是药物发现、开发和个性化医疗的未来。