Currently, there is a need for strategies that mitigate acute radiation-induced gastrointestinal syndrome (RIGS). The risk of large populations encountering radiation exposure is real and growing. Although a few drugs are available which can protect radiation injury if applied prior to radiation exposure, to date there are no agents available which can be applied 24 hr post-exposure to mitigate the acute radiation syndrome. The high radiosensitivity of the intestinal epithelium increases susceptibility to RIGS; and with mortality within 10-15 days there is limited time for therapeutic intervention. We have developed a human peripheral blood mono nuclear cell derived macrophage committed progenitor (MCP) cell therapy which can mitigate RIGS and improve survival when applied 24 hr after an otherwise lethal dose of radiation exposure. These progenitor cells are modulated ex-vivo to increase expression of WNT ligand, a major paracrine signal for intestinal epithelial regeneration. In this project we will fully characterize this novel cell therapy with a determination of an optimum dose and schedule for mitigation of RIGS. We will examine the general applicability of this strategy in young and radiosensitive animals. Finally we will evaluate the involvement of MCP derived WNT signaling in repair and regeneration of intestinal stem cells.

Public Health Relevance

The proposed research will characterize a type of cell therapy as a countermeasure against radiation injury with efficacy at 24 hours after radiation exposure. This proposal will also define the mechanism of action of the countermeasure which will provide data necessary for product licensure requirements according to the FDA Animal Rule. Successful completion of this project will lead to the development of this cell therapy as a new medical countermeasure to treat injuries resulting from a radiation or nuclear accident.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AI138323-04
Application #
10116168
Study Section
Special Emphasis Panel (ZAI1)
Program Officer
Rios, Carmen I
Project Start
2018-03-07
Project End
2023-02-28
Budget Start
2021-03-01
Budget End
2022-02-28
Support Year
4
Fiscal Year
2021
Total Cost
Indirect Cost
Name
University of Kansas
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
016060860
City
Kansas City
State
KS
Country
United States
Zip Code
66160