# A spatially organized microphysiological model of a human lymph node

> **NIH NIH U01** · UNIVERSITY OF VIRGINIA · 2021 · $640,367

## Abstract

PROJECT SUMMARY/ABSTRACT
 The potential to model the human body on a microchip offers tantalizing hope of predictive drug testing
and unprecedented control for mechanistic experiments. However, existing organ-on-chip systems exclude the
lymph node (LN), the small and highly organized organ that initiates adaptive immune responses. Without a LN,
the induction and development of antibody- or cell-mediated immunity is also largely absent. Other available in
vitro LN-mimetic systems do not yet address the crucial spatial organization and local microenvironment of this
tissue. As most humans want to keep their LNs, an experimentally tractable, biomimetic model of the dynamics
and organization of this organ is needed both for mechanistic studies and to test new therapies.
 In this project, our uniquely qualified team of engineers and immunologists will develop and
validate the first spatially organized, 3D-cultured microphysiological model of a lymph node (LN-chip),
featuring biomimetic cellular organization and fluid flow. In Aim 1, we will establish methods to micropattern
primary human immune cells in 3D culture inside a microfluidic chip, using on-chip photolithography of photo-
crosslinkable gels. This innovative approach provides simultaneous control over cellular distribution, local matrix
composition, and fluid flow, to replicate diffusion and migration distances for 3D cell-cell interactions. We will
optimize patterning and culture conditions to maintain viability for 7 – 28 days, preserve T and B cell response
to simple stimuli, and test multiple materials for the microfluidic housing. In Aim 2, we will identify the best strategy
to achieve biomimetic lymph node organization by comparing the robustness of microstructure obtained by
patterning chemokine gradients, stromal/endothelial cells, or lymphocytes. We will also determine the optimal
fluid flow conditions for biomimetic function. In Aim 3, we will establish conditions for productive T-B cell
interactions on the LN-chip leading to differentiation and production of long-lived, high-affinity antibodies.
Responses on the LN-chip will be directly compared to those of ex vivo cultured human tonsils, to provide
definitive data on the relevance of the model to human immunity. Finally, we will employ CRISPR/Cas9 gene
editing to test the extent to which the LN-chip recapitulates human disease caused by defects in T—B interaction.
 In summary, this U01 project will produce validated procedures for robust and reproducible assembly of
the first spatially organized LN-chip, including specific guidelines for inclusion of stromal cells and lymphocytes,
and benchmarking against well-defined human T- B interactions. The platform will be broadly applicable to model
inflammatory and autoimmune diseases, test vaccination strategies, and answer mechanistic questions about
LN function. It will be compatible with in-line coupling to other organs-on-chip from the Tissue Chip consortium,
and will allow for direc...

## Key facts

- **NIH application ID:** 10239046
- **Project number:** 5U01EB029127-03
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Rebecca R Pompano
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $640,367
- **Award type:** 5
- **Project period:** 2019-09-17 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10239046

## Citation

> US National Institutes of Health, RePORTER application 10239046, A spatially organized microphysiological model of a human lymph node (5U01EB029127-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10239046. Licensed CC0.

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