Scale up and In-vitro Testing of Exosomes for Regenerative Medicine Applications

干细胞分泌的外泌体作为21世纪医疗保健的候选治疗平台正受到极大的关注。这是因为越来越多的外泌体研究表明，它们可以在靶细胞中驱动理想的行为变化，改变或逆转病理过程。外泌体的潜在应用是广泛的，包括无细胞再生医学和癌症治疗的另一端。为了充分了解外泌体的治疗功能，有必要系统地表征从一系列不同细胞培养方案中分离的外泌体群体。对于商业开发至关重要的是，产生与治疗相关数量的外泌体也是必要的，这需要创建一个细胞培养过程，可以扩大规模以提供工业数量的外泌体产品。利用模拟工业生物反应器技术的实验规模生物反应器，该项目将利用再生药物生物过程工程方面的专业知识，以扩大干细胞及其外泌体的生产规模。然后，它将使用微流体和分析技术进行外泌体效力的体外测试。这可以使用自动化的灌注细胞培养设备来实现，该设备支持外泌体如何影响3D显微组织的行为的原位监测。3D微组织将使用细胞和生物材料创建自组装组织。微流控装置将导致最小的操作误差和增加的测量一致性。

Stem cell-secreted exosomes are gaining significant attention as a candidate therapeutic platform for 21st century healthcare. This is because a growing body of research into exosomes has revealed that they can drive desirable behavioural changes in target cells, modifying or reversing pathological processes. The potential applications of exosomes are broad and include cell-free regenerative medicine at one end of the spectrum and cancer therapeutic at the other. To fully understand the therapeutic repertoire of exosomes, it is necessary to systematically characterise exosome populations isolated from a range of different cell culture scenarios. Critical for commercial development, it is also necessary to generate exosomes in therapeutically relevant quantities, which requires the creation of a cell culture process that can be scaled up to deliver industrial quantities of exosome product. Using bench-scale bioreactors that mimic industrial bioreactor technologies, this project will draw on expertise across bioprocess engineering for regenerative medicines in order to scale up production of stem cells and their exosomes. It will then use microfluidics and analytics for in vitro testing of exosome potency. This can be achieved using automated, perfused cell culture devices that support in situ monitoring of how exosomes influence the behaviour of 3D microtissues. 3D microtissues will be created using cells and biomaterials to create self-assembled tissues. The microfluidic devices will result in minimal operator error and increased measurement consistency.