# 3D biomimetic lymph node engineered extracellular vesicles for understanding the heterogeneity of adaptive immunity

> **NIH NIH R35** · UNIVERSITY OF FLORIDA · 2023 · $7,595

## Abstract

ABSTRACT
Understanding how immune-heterogeneity leverages cellular diversity to achieve the adaptivity and flexibility in
immune-responses is a core challenge that has not been well studied, largely due to the lack of a valid immunity
tissue model for investigation of cellular communications. Recent discovery of trafficking vesicles since 2013
Nobel Prize of Medicine shined the light on the new avenue for understanding long-distance, non-contact cellular
communications in modulating immunity. However, the study of such diverse and nano-sized vesicles, namely
exosomes, is extremely challenging, due to immense difficulties in differentiating dynamic and heterogeneous
vesicle populations presented in the in vivo system. Our research work addresses key technology gaps by
developing a series of tool sets, including high-efficient and high-throughput microfluidic approach for exosome
isolation, subtyping, molecular engineering and transfection, and nano-delivery. Recently, we observed that
molecular packaging of secreted exosomes is highly variable upon the change of cellular culture environment
as well as surrounding community. The in vitro investigations with 2D cell culture systems are incapable of
interpreting in vivo exosome immunity modulation mechanism. We hypothesize that a 3D biomimetic lymph node
tissue system could serve as the in vivo -like tissue model for effectively studying in vivo exosome molecular
packaging and secretion dynamics upon stimulations, for interconnecting exosomal cargoes with cellular level
responses. This five-year study will focus on three key challenges for precisely elucidating immune-modulation
at the molecular level via the exosome route: 1) Develop a 3D, programmable biomimetic lymph node tissue
foundry with well-defined immunological adaptations for mimicking in vivo immune tissue microenvironment; 2)
Develop a single cell single exosome study approach for highly sensitive detection and subtyping of single
exosome populations with dynamic and statistical significance for understanding immunity heterogeneity; 3)
Discover motifs that can selectively pack immuno-stimulating microRNAs, as well as the MHC-binding peptides
into exosomes for targeted immunity modulation, which can establish the interconnection of cargo internalization
with cellular level responses. The long-term goal is to advance our understanding in immunity regulation
heterogeneity and eventually be able to precisely programme immune responses at the molecular precision.

## Key facts

- **NIH application ID:** 10808671
- **Project number:** 3R35GM133794-04S2
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Mei He
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $7,595
- **Award type:** 3
- **Project period:** 2019-09-20 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10808671

## Citation

> US National Institutes of Health, RePORTER application 10808671, 3D biomimetic lymph node engineered extracellular vesicles for understanding the heterogeneity of adaptive immunity (3R35GM133794-04S2). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10808671. Licensed CC0.

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