In the development of novel pharmaceutics and cell-mediated therapeutics, the immune system has to be well considered as part of the response mechanism or as a potential collateral for drug toxicity. To reduce the attrition of such developments, the interaction of immune cells with drugs and/or with other cell types should be mechanistically investigated.
As the lymph node (LN) is the integrating center for immune cells, whereby the body invokes immune responses against foreign substances, it is an ideal site for the study of drug interaction with biological components. We have developed a novel microfluidic platform replicating the LN microenvironment, called LN-on-Chip, to facilitate biological investigations of immune cellular kinetics, cell-cell interactions, cell-drug interactions, and sampling. We recreated the biological scaffold and reintroduced the cellular residents in an in vivo-like distribution into the device. We showed that the developed LN-on-Chip incorporates key features of the native human LN, namely the compartmentalization of immune cells within distinct structural domains and the replication of lymphatic fluid flow pattern supports 3D cell culture in biomimetic matrices, and sustains high rates of cell viability over the typical timeframe of immunotoxicity experiments. Further, we demonstrated enhanced proliferation of immune cell coculture in a low-flow perfusion LN system and observed immune cellular interactions. The ultimate goal of this platform is to enable investigations into the effects of pharmaceutics to downstream immunology in more physiologically relevant microenvironments, thus, contributing to increased safety, lowered cost, and shorter cycles for drug development.
