Bioengineered lymph nodes offer window into human immunity

A new method to keep human lymph node tissue alive and functioning outside the body for several days could give researchers a much clearer view of how our immune system responds to infections, vaccines and cancer, without the need for  preclinical modelling or over-simplified laboratory models.

Developed by researchers at the College of Design and Engineering (CDE) at the National University of Singapore (NUS) and the National Cancer Centre Singapore, the developed bioengineering approach involves embedding thin slices of lymph node tissue in a soft gel that mimics the body’s natural environment. The study was published on 29 August 2025 in the Cell Press journal, Trends in Biotechnology.

“This innovative approach preserves the original architecture and functions of the tissue for at least a week, enabling detailed, real-time studies of how immune cells behave in response to specific immune perturbations,” said Assistant Professor Eliza Fong from the Department of Biomedical Engineering at NUS CDE, who co-led the study.

Lymph nodes are small, bean-shaped structures that act as command centres for the immune system. Until now, most research has relied on preclinical models or simplified cell cultures, which often fail to reflect the complexity of human immunity.

“Lymph nodes are key to how our immune system detects and responds to disease, but they’ve been notoriously hard to study outside the body,” said Professor N Gopalakrishna Iyer, Senior Consultant at the National Cancer Centre Singapore and co-lead of this study. “Our model keeps the tissue alive and working long enough for us to see how real immune responses unfold in a human setting.”

Hydrogel scaffold

In conventional laboratory setups, lymph node tissue typically breaks down within a day or two, rapidly losing both its structure and function. To overcome this, the team embedded resected non-involved lymph node slices from head and neck cancer patients into a bioengineered hyaluronan-based hydrogel. The hydrogel, previously developed by the team to preserve tumour slices ex vivo, acts as a scaffold that supports the tissue and reduces cell loss.

Compared to free-floating samples, the hydrogel-embedded tissue maintained its size, structure and viability for significantly longer. More importantly, it continued to function. When the tissue was exposed to cancer cells from the same patient or to a COVID-19 mRNA vaccine, it responded in ways that showed the immune system was working, releasing signaling molecules, activating immune cells, and in some cases even producing antibodies, especially after several days in culture.

One sample even showed an active immune response before any vaccine exposure, likely due to prior infection or vaccination. This highlighted the model’s ability to reflect a patient’s unique immune history.

“This platform gives us a much more accurate picture of human immune responses, and how they can vary from person to person,” said Asst Prof Fong. “That could be extremely valuable for developing personalised vaccines or cancer treatments.”

While the model currently supports tissue function for about a week, the researchers are working to extend that timeframe and add features such as lymph flow. In future, they say, the system could be adapted for screening of cancer or infectious disease vaccines and even immunotherapies, offering a faster and more human-relevant alternative to preclinical testing.

“Our ultimate goal is to build more predictive models of the human immune system,” said Asst Prof Fong. “This is a significant step in that direction, and one that brings us closer to more effective, personalised ways of treating disease.”