# Dkk1-Endothelial Progenitor Cell Treatment for the Mitigation of Hematopoietic Radiation Injury

> **NIH NIH U01** · MEDICAL COLLEGE OF WISCONSIN · 2021 · $780,249

## Abstract

Project Summary
This project proposes to assess whether administration of Dkk1-treated endothelial progenitor cells (Dkk1-
EPCs) mitigates radiation injury to the bone marrow by promoting concomitant vascular and hematopoietic
recovery. The ultimate goal of this work is to develop a cell therapy that can be administered >48 hours after
injury to rescue victims of radiation exposure from death due to hematopoietic toxicities such as infection,
anemia, and hemorrhage. This is clinically relevant as there are likely to be several hundred thousand victims
with acute hematopoietic toxicities if a large-scale nuclear or radiological terror attack were to occur. In a mass
casualty scenario, treatment is likely to be delayed due to the large volume of victims; however, the current
standard of care Neupogen (G-CSF) only has proven survival benefit when administered with the first 24
hours. Therefore, we propose to characterize a novel cell-based rescue therapy for mitigation of radiation
injury to the bone marrow.
Past work from our laboratory and others has shown that infusion of endothelial cells can accelerate
hematopoietic recovery and rescue lethally irradiated mice from death due to hematopoietic syndrome. In this
proposal, we show that pre-treatment with Dkk1 stimulates endothelial cells to produce regenerative and
angiogenic factors such as epidermal growth factor. Furthermore, we show that allogeneic transplantation of
Dkk1-treated EPCs (Dkk1-EPCs) significantly improved vascular and hematopoietic recovery following 5 Gy
total body irradiation compared to saline or EPC treatment alone. Based on these findings, we hypothesize
that Dkk1-EPCs are a potential cellular therapeutic for the mitigation of hematopoietic toxicities in ARS vicitims.
To test this hypothesis, we propose the following specific aims: 1) Determine whether systemic administration
of Dkk1-EPCs improves survival in lethally irradiated mice. 2) Determine whether Dkk1-EPCs mitigate injury to
irradiate human BM CD34+ cells. 3) Develop a clinical resource of human EPCs. 4) Determine the cellular
mechanisms through which Dkk1-EPCs promote regeneration in irradiated mice.

## Key facts

- **NIH application ID:** 10202467
- **Project number:** 5U01AI138331-05
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** Heather A Himburg
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $780,249
- **Award type:** 5
- **Project period:** 2018-03-12 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10202467

## Citation

> US National Institutes of Health, RePORTER application 10202467, Dkk1-Endothelial Progenitor Cell Treatment for the Mitigation of Hematopoietic Radiation Injury (5U01AI138331-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10202467. Licensed CC0.

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