# Biobank of small extracellular vesicles for pediatric sepsis

> **NIH NIH R21** · CINCINNATI CHILDRENS HOSP MED CTR · 2024 · $219,338

## Abstract

PROJECT SUMMARY
Sepsis is a dysregulated host response to an infection and can lead to multiple organ dysfunction syndrome
(MODS). There are no effective treatments for sepsis-induced MODS most likely because of the heterogeneity
of the syndrome. Delineating MODS endotypes and molecular signatures of organ failures may lead to a better
understanding of the mechanisms involved in sepsis heterogeneity and allow for personalized treatment
strategies. It is difficult, however, to obtain clinical specimens from critically ill patients that would enable
investigations into organ-specific mechanistic changes. Extracellular vesicles (EVs) are spherical microparticles
enclosed by bilayer phospholipid membranes. Exosomes or small EVs (sEVs) are a subtype of EV formed by
endosomal biogenesis. Small EVs can be released from almost any cell type into a variety of bodily fluids and
contain many cellular components. The cell-specific cargo can serve as cell-to-cell communicators and be taken
up by distant cells which can affect the inflammatory profile. Our preliminary data show that sEVs harvested from
serum of pediatric patients with sepsis have a distinct pro-inflammatory trait compared to sEVs of children without
sepsis and in vitro sEVs from septic patients can induce atypical inflammatory responses in immune cells. Since
circulating sEVs manifest characteristics of the cell of origin, they have been used as liquid biopsy. Thus, sEVs
hold potential as useful biomarker for organ-specific changes. There are no available biorepositories of sEVs for
pediatric sepsis research, in part, because of the lack of standardized methodology for sEV isolation. The overall
goal of our proposal is to establish standardized procedures for reliable biorepositories for sEV biomarker
research in critically ill patients with sepsis. This proposal will prove the hypothesis that quality and consistency
of isolation and purification protocols of plasma and serum samples enable setting-up reliable biorepositories for
future research on sEVs in sepsis. We will take advantage of two large critical care-division based repositories
which has biospecimens from pediatric critically ill septic and non-septic studies. The R21 phase Aim 1 is to
develop a methodology for sample collection and isolation of sEVs with high yield and purity and Aim 2 is to
demonstrate suitability of banked sEVs for high throughput analyses of RNA cargo profile. Once milestones for
the R21 phase are met we will proceed to the R33 phase to retrospectively characterize sEV endotypes in
critically ill patients with specific organ injuries (Aim 3) and then prospectively determine whether patients can
be classified based on their sEV characteristics. Results from these investigations will allow for the novel
development of a biorepository of sEVs in pediatric sepsis. This biorepository will enable investigators to explore
organ-specific molecular signatures for mechanistic studies of sEVs.

## Key facts

- **NIH application ID:** 10909309
- **Project number:** 5R21GM151734-02
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Jennifer Melissa Kaplan
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $219,338
- **Award type:** 5
- **Project period:** 2023-08-17 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10909309

## Citation

> US National Institutes of Health, RePORTER application 10909309, Biobank of small extracellular vesicles for pediatric sepsis (5R21GM151734-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10909309. Licensed CC0.

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