Department of Chemistry, University of Virginia, Charlottesville, VA, USA.
Lab Chip. 2019 Mar 13;19(6):1013-1026. doi: 10.1039/c8lc00957k.
Experimentally accessible tools to replicate the complex biological events of in vivo organs offer the potential to reveal mechanisms of disease and potential routes to therapy. In particular, models of inter-organ communication are emerging as the next essential step towards creating a body-on-a-chip, and may be particularly useful for poorly understood processes such as tumor immunity. In this paper, we report the first multi-compartment microfluidic chip that continuously recirculates a small volume of media through two ex vivo tissue samples to support inter-organ cross-talk via secreted factors. To test on-chip communication, protein release and capture were quantified using well-defined artificial tissue samples and model proteins. Proteins released by one sample were transferred to the downstream reservoir and detectable in the downstream sample. Next, the chip was applied to model the communication between a tumor and a lymph node, to test whether on-chip dual-organ culture could recreate key features of tumor-induced immune suppression. Slices of murine lymph node were co-cultured with tumor or healthy tissue on-chip with recirculating media, then tested for their ability to respond to T cell stimulation. Interestingly, lymph node slices co-cultured with tumor slices appeared more immunosuppressed than those co-cultured with healthy tissue, suggesting that the chip may successfully model some features of tumor-immune interaction. In conclusion, this new microfluidic system provides on-chip co-culture of pairs of tissue slices under continuous recirculating flow, and has the potential to model complex inter-organ communication ex vivo with full experimental accessibility of the tissues and their media.
实验上可及的工具可复制体内器官的复杂生物学事件，从而有可能揭示疾病的机制和潜在的治疗途径。特别是，器官间通讯模型作为创建芯片上器官的下一个重要步骤正在出现，对于肿瘤免疫等理解较差的过程可能特别有用。在本文中，我们报告了第一个多腔室微流控芯片，该芯片通过两个离体组织样本连续再循环小体积介质，以通过分泌因子支持器官间串扰。为了测试芯片上的通讯，使用明确定义的人工组织样本和模型蛋白来定量测量蛋白质的释放和捕获。一个样本释放的蛋白质被转移到下游储液器中，并可在下游样本中检测到。接下来，将该芯片应用于模拟肿瘤和淋巴结之间的通讯，以测试芯片上的双器官培养是否可以再现肿瘤诱导免疫抑制的关键特征。将鼠淋巴结切片与肿瘤或健康组织在带有再循环介质的芯片上共培养，然后测试其对 T 细胞刺激的反应能力。有趣的是，与肿瘤切片共培养的淋巴结切片比与健康组织共培养的淋巴结切片更具免疫抑制性，这表明该芯片可能成功地模拟了肿瘤免疫相互作用的某些特征。总之，这种新的微流控系统提供了在连续再循环流动下共培养成对组织切片的芯片上方法，并且有可能在体外模拟复杂的器官间通讯，具有组织及其介质的完全实验可及性。
