Lymph node on a chip: New immune system model may enhance precision medicine research

Scientists with the Fralin Biomedical Research Institute at VTC have created an engineered model of the supportive tissue found within a lymph node to study human health.  

Working with scientists at the University of Virginia, the researchers are building a bioengineered model of a human lymph node, which performs essential roles in the immune system throughout the body. 

The goal of the research, which published in April in APL Bioengineering, is to provide scientists with a model that accurately mirrors dynamic fluid flow — a natural part of how lymph nodes work.

The model functions like a lymph node-on-a-chip, recreating aspects of the human lymph node environment — including fluid flow and cellular interactions — to study immune behavior outside the body.

Developing laboratory models is critical to better investigate immune system responses and test new treatments outside of the body.

An engineered lymph node could advance health research in a number of ways:

• It could lower the cost of biomedical experiments, as compared with mouse models.
• Because they are engineered with human tissue, the models may be more accurate and more translatable to human health research.
• In addition, the model can be used to personalize care for individual patients and lead to safer, more effective strategies to boost the immune system in a wide range of diseases.

What diseases could this help inform? 

“Cancer metastasis is an obvious area since lymph nodes are a major site of tumor spread,” said Professor Jennifer Munson, the paper’s author and director of the institute’s Cancer Research Center in Roanoke. “But we’re also looking at areas such as anti-tumor immunity, vaccine testing, viral infections, and autoimmune disorders.”

Munson leads research on fluid flow in disease and is working with the model to study breast cancer progression and Alzheimer’s disease.

In this research, she focuses on the stroma. Stromal cells — which include fibroblastic reticular and endothelial cells — are the framework within a lymph node that provide structure, guide immune cell movement, and can influence the immune response. 

The lymph node stroma model offers a platform to test complex fluid flow and retention of T cells, which support the immune system and fight disease. 

The research also points to the importance of considering fluid flow when building other cell models. Existing in vitro models focus on interactions between T cells, B cells, and dendritic cells, rather than stromal cells.

The research team modeled two different environments in the study, one with inflammation and one without. During inflammation, fluid flow between cells in the lymph nodes drastically increases. 

“We found that they behaved differently. The inflammation tended to trap the cells,” Munson said.

Munson, who is also a professor in the Department of Biomedical Engineering and Mechanics in the College of Engineering, was part of a team that won a challenge prize competition, sponsored by the National Institutes of Health, whose goal was to fast-track development of new biomedical research approaches that could complement, or replace, traditional models, including animal research.

The team's model proposed using cells from human donors that are cultured to form tiny replicas of brain, lymph node, and fat tissue. The current study builds on those concepts. Engineered tissue models are a step toward understanding disease progression and improving pre-clinical drug screening.

The research was supported by grants from the National Center for Advancing Translational Sciences, and the National Institute on Aging, all part of the National Institutes of Health. The study also received support from the Red Gates Foundation and Virginia Tech's Institute for Critical Technology and Applied Science.