# Exosome educated monocytes for acute radiation syndrome

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2022 · $525,256

## Abstract

PROJECT SUMMARY/ABSTRACT
Finding novel therapies for treatment of radiation-induced toxicities is of value to not only patients who are
receiving radiotherapy for different conditions, but also to national security due to risk of terrorism attacks.
There is urgent need to develop therapies than can be administered quickly after exposure to minimize the
effects of radiation and enhance immune recovery. Preclinical models have informed a great deal of our
current clinical practice in managing acute radiation syndrome (ARS). These models can be used to test and
develop new cellular therapies. Choosing the proper cell subset, engineering it to produce the necessary
cytokines, and understanding how the cells interact with other hematopoietic and immune cells in vivo after
infusion are all critical factors in developing a proper cell-based therapy for ARS. Our group has previously
characterized an alternatively activated, high IL-6 producing human macrophage subset called mesenchymal
stem cell (MSC)-educated macrophages that can enhance survival from lethal ARS using a xenogeneic mouse
model as compared to infusions of MSCs or macrophages alone. We have simplified generation of these cells
by using exosomes from lipopolysaccharide-stimulated MSCs to educate monocytes into a radioprotective cell
subset. The long-term objectives of this proposal are to use MSC-exosomes to improve the generation and
efficacy of radioprotective cells and define their mechanism of radioprotection in preclinical models of ARS. We
will test the hypotheses that: (1) LPS-high exosome-educated monocytes (LPS-high EEMos) can mediate
radioprotection as an allogeneic cell therapy through production of IL-6; (2) LPS-high EEMos protect the host
from ARS by trafficking to radiosensitive organs, like bone marrow, and can be tracked by magnetic resonance
imaging (MRI); and (3) LPS-mimetics can be used to stimulate MSC exosome production that generate EEMos
through let-7b microRNA secretion. Success of any of the individual aims will be a major advance in
understanding how monocytes impact blood cell development after ARS. Translation of the entire proposal will
lead to an innovative, mechanistic understanding of a new cellular therapy for treating ARS.

## Key facts

- **NIH application ID:** 10458706
- **Project number:** 5R01HL153721-02
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Christian Capitini
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $525,256
- **Award type:** 5
- **Project period:** 2021-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10458706

## Citation

> US National Institutes of Health, RePORTER application 10458706, Exosome educated monocytes for acute radiation syndrome (5R01HL153721-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10458706. Licensed CC0.

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