Selden Clare, Fuller Barry
Institute for Liver and Digestive Health, Division of Medicine, Faculty of Medical Sciences, University College London, Royal Free Hospital Campus, Rowland Hill Street, Hampstead, London NW3 2PF, UK.
Department of Nanotechnology, Division of Surgery & Interventional Science, Faculty of Medical Sciences, University College London, London NW3 2QG, UK.
Bioengineering (Basel). 2018 Apr 24;5(2):32. doi: 10.3390/bioengineering5020032.
Micro and small bioreactors are well described for use in bioprocess development in pre-production manufacture, using ultra-scale down and microfluidic methodology. However, the use of bioreactors to understand normal and pathophysiology by definition must be very different, and the constraints of the physiological environment influence such bioreactor design. This review considers the key elements necessary to enable bioreactors to address three main areas associated with biological systems. All entail recreation of the in vivo cell niche as faithfully as possible, so that they may be used to study molecular and cellular changes in normal physiology, with a view to creating tissue-engineered grafts for clinical use; understanding the pathophysiology of disease at the molecular level; defining possible therapeutic targets; and enabling appropriate pharmaceutical testing on a truly representative organoid, thus enabling better drug design, and simultaneously creating the potential to reduce the numbers of animals in research. The premise explored is that not only cellular signalling cues, but also mechano-transduction from mechanical cues, play an important role.
微型和小型生物反应器在预生产制造的生物工艺开发中已有详细描述，采用超规模缩小和微流控方法。然而，从定义上讲，使用生物反应器来理解正常生理和病理生理必然大不相同，生理环境的限制会影响此类生物反应器的设计。本综述考虑了使生物反应器能够解决与生物系统相关的三个主要领域所需的关键要素。所有这些都需要尽可能忠实地重现体内细胞生态位，以便它们可用于研究正常生理中的分子和细胞变化，旨在创建用于临床的组织工程移植物；在分子水平上理解疾病的病理生理；确定可能的治疗靶点；并在真正具有代表性的类器官上进行适当的药物测试，从而实现更好的药物设计，同时创造减少研究中动物数量的潜力。所探讨的前提是，不仅细胞信号线索，而且机械线索的机械转导也起着重要作用。
