Plug-and-Play Lymph Node-on-Chip: Secondary Tumor Modeling by the Combination of Cell Spheroid, Collagen Sponge and T-Cells

Towards the improvement of the efficient study of drugs and contrast agents, the 3D microfluidic platforms are currently being actively developed for testing these substances and particles in vitro. Here, we have elaborated a microfluidic lymph node-on-chip (LNOC) as a tissue engineered model of a secondary tumor in lymph node (LN) formed due to the metastasis process. The developed chip has a collagen sponge with a 3D spheroid of 4T1 cells located inside, simulating secondary tumor in the lymphoid tissue. This collagen sponge has a morphology and porosity comparable to that of a native human LN. To demonstrate the suitability of the obtained chip for pharmacological applications, we used it to evaluate the effect of contrast agent/drug carrier size, on the penetration and accumulation of particles in 3D spheroids modeling secondary tumor. For this, the 0.3, 0.5 and 4 mu m bovine serum albumin (BSA)/tannic acid (TA) capsules were mixed with lymphocytes and pumped through the developed chip. The capsule penetration was examined by scanning with fluorescence microscopy followed by quantitative image analysis. The results show that capsules with a size of 0.3 mu m passed more easily to the tumor spheroid and penetrated inside. We hope that the device will represent a reliable alternative to in vivo early secondary tumor models and decrease the amount of in vivo experiments in the frame of preclinical study.

Automated summary

In order to enhance the study of drugs and contrast agents, 3D microfluidic platforms are being actively developed for in vitro testing. A microfluidic lymph node-on-chip (LNOC) was created as a tissue engineered model of a secondary tumor in the lymph node. The developed chip demonstrated suitability for pharmacological applications and showed that smaller size capsules had better penetration into the tumor spheroid. This device could potentially replace in vivo models for early secondary tumors and reduce the need for in vivo experiments in preclinical studies.