# Project 2 Endothelial Cell-Derived Extracellular Vesicles for Mitigation of the Hematopoietic Acute Radiation Syndrome

> **NIH NIH U19** · DUKE UNIVERSITY · 2022 · $356,830

## Abstract

ABSTRACT
 The misuse of ionizing radiation or nuclear devices as weapons of terrorism has been recognized as a
major U.S. public health threat. The greatest risk to these victims of radiation exposure is the hematopoietic
acute radiation syndrome (H-ARS), which results in life-threatening complications such as infections and
refractory bleeding. Specific therapies directed at H-ARS to accelerate hematopoietic regeneration following
radiation injury have been few. Since marrow endothelial cells can govern hematologic recovery after
irradiation without homing to the bone marrow, endothelial cells can mediate their radioprotective effects
through elaboration of hematopoietic cytokines or soluble factors. Another mechanism of cellular
communication is through transfer of proteins and nucleic materials via secretion of extracellular vesicles
(EVs). EVs range in size from 100-250 nm and bear both nucleic acids and proteins that have potential to
regulate neighboring cells. We hypothesize that ECs exert their regenerative effects through EVs. We have
shown that treatment of irradiated hematopoietic stem/progenitor cells with either syngeneic or allogeneic EVs
from genetically distinct mice results in comparable expansion of the stem cell pool, suggesting they could be
immunologically tolerant. Compared to control mice treated with granulocyte colony stimulating factor (G-CSF),
it is possible that EVs are at least comparable and are likely superior to G-CSF for prolonging survival after
lethal-dose irradiation. Our overriding goal is to demonstrate the radiotherapeutic capacity of EVs. In doing so,
we will develop a cellular-based therapy for H-ARS with potential for off-the-shelf delivery to victims in the
setting of a mass casualty disaster.

## Key facts

- **NIH application ID:** 10468618
- **Project number:** 5U19AI067798-18
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Phuong Linh Doan
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $356,830
- **Award type:** 5
- **Project period:** 2005-09-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10468618

## Citation

> US National Institutes of Health, RePORTER application 10468618, Project 2 Endothelial Cell-Derived Extracellular Vesicles for Mitigation of the Hematopoietic Acute Radiation Syndrome (5U19AI067798-18). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10468618. Licensed CC0.

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