Multi-Compartment Lymph-Node-on-a-Chip Enables Measurement of Immune Cell Motility in Response to Drugs.
Nicholas HallforsAya ShantiJiranuwat SapudomJeremy TeoGeorg PetroianuSungMun LeeLourdes PlanellesCesare StefaniniPublished in: Bioengineering (Basel, Switzerland) (2021)
Organs On-a-Chip represent novel platforms for modelling human physiology and disease. The lymph node (LN) is a relevant immune organ in which B and T lymphocytes are spatially organized in a complex architecture, and it is the place where the immune response initiates. The present study addresses the utility of a recently designed LN-on-a-chip to dissect and understand the effect of drugs delivered to cells in a fluidic multicellular 3D setting that mimics the human LN. To do so, we analyzed the motility and viability of human B and T cells exposed to hydroxychloroquine (HCQ). We show that the innovative LN platform, which operates at a microscale level, allows real-time monitoring of co-cultured B and T cells by imaging, and supports cellular random movement. HCQ delivered to cells through a constant and continuous flow induces a reduction in T cell velocity while promotes persistent rotational motion. We also find that HCQ increases the production of reactive oxygen species in T cells. Taken together, these results highlight the potential of the LN-on-a-chip to be applied in drug screening and development, and in cellular dynamics studies.
Keyphrases
- lymph node
- endothelial cells
- high throughput
- immune response
- induced apoptosis
- circulating tumor cells
- induced pluripotent stem cells
- reactive oxygen species
- cell cycle arrest
- neoadjuvant chemotherapy
- emergency department
- high resolution
- biofilm formation
- squamous cell carcinoma
- cell death
- cystic fibrosis
- toll like receptor
- signaling pathway
- inflammatory response
- early stage
- photodynamic therapy
- pseudomonas aeruginosa
- single cell
- sentinel lymph node
- drug induced
- endoplasmic reticulum stress
- oxidative stress
- radiation therapy
- locally advanced
- blood flow
- adverse drug