Miller Paula G, Wang Ying I, Swan Glen, Shuler Michael L
Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, 14853.
Robert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY, 14853.
Biotechnol Prog. 2017 Sep;33(5):1257-1266. doi: 10.1002/btpr.2512. Epub 2017 Jun 21.
Transporting living complex cellular constructs through the mail while retaining their full viability and functionality is challenging. During this process, cells often suffer from exposure to suboptimal life-sustaining conditions (e.g. temperature, pH), as well as damage due to shear stress. We have developed a transport device for shipping intact cell/tissue constructs from one facility to another that overcomes these obstacles. Our transport device maintained three different cell lines (Caco2, A549, and HepG2 C3A) individually on transwell membranes with high viability (above 97%) for 48 h under simulated shipping conditions without an incubator. The device was also tested by actual overnight shipping of blood brain barrier constructs consisting of human induced pluripotent brain microvascular endothelial cells and rat astrocytes on transwell membranes to a remote facility (approximately 1200 miles away). The blood brain barrier constructs arrived with high cell viability and were able to regain full barrier integrity after equilibrating in the incubator for 24 h; this was assessed by the presence of continuous tight junction networks and in vivo-like values for trans-endothelial electrical resistance (TEER). These results demonstrated that our cell transport device could be a useful tool for long-distance transport of membrane-bound cell cultures and functional tissue constructs. Studies that involve various cell and tissue constructs, such as the "Multi-Organ-on-Chip" devices (where multiple microscale tissue constructs are integrated on a single microfluidic device) and studies that involve microenvironments where multiple tissue interactions are of interest, would benefit from the ability to transport or receive these constructs. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1257-1266, 2017.
在通过邮寄运输活的复杂细胞构建体的同时保持其完全的活力和功能具有挑战性。在此过程中,细胞常常会因暴露于次优的维持生命条件(如温度、pH值)以及受到剪切应力的损伤。我们开发了一种运输装置,用于将完整的细胞/组织构建体从一个设施运送到另一个设施,从而克服了这些障碍。我们的运输装置在模拟运输条件下且无培养箱的情况下,能使三种不同的细胞系(Caco2、A549和HepG2 C3A)在Transwell膜上分别保持高活力(高于97%)达48小时。该装置还通过将由人诱导多能脑微血管内皮细胞和大鼠星形胶质细胞组成的血脑屏障构建体在Transwell膜上实际隔夜运送到一个偏远设施(约1200英里外)进行了测试。血脑屏障构建体到达时细胞活力很高,在培养箱中平衡24小时后能够恢复完全的屏障完整性;这通过连续紧密连接网络的存在以及跨内皮电阻(TEER)的体内样值来评估。这些结果表明,我们的细胞运输装置可能是用于膜结合细胞培养物和功能性组织构建体长距离运输的有用工具。涉及各种细胞和组织构建体的研究,如“多器官芯片”装置(其中多个微尺度组织构建体集成在单个微流控装置上)以及涉及多种组织相互作用的微环境的研究,将受益于运输或接收这些构建体的能力。© 2017美国化学工程师学会生物技术进展,33:1257 - 1266,2017年。