Cellular Therapies for Treatment of Radiation Injury: Report from a NIH/NIAID and IRSN Workshop.

Abstract:

:In recent years, there has been increasing concern over the possibility of a radiological or nuclear incident occurring somewhere in the world. Intelligence agencies frequently report that terrorist groups and rogue nations are seeking to obtain radiological or nuclear weapons of mass destruction. In addition, there exists the real possibility that safety of nuclear power reactors could be compromised by natural (such as the tsunami and subsequent Fukushima accident in Japan in March, 2011) or accidental (Three Mile Island, 1979 and Chernobyl, 1986) events. Although progress has been made by governments around the world to prepare for these events, including the stockpiling of radiation countermeasures, there are still challenges concerning care of patients injured during a radiation incident. Because the deleterious and pathological effects of radiation are so broad, it is desirable to identify medical countermeasures that can have a beneficial impact on several tissues and organ systems. Cellular therapies have the potential to impact recovery and tissue/organ regeneration for both early and late complications of radiation exposure. These therapies, which could include stem or blood progenitor cells, mesenchymal stromal cells (MSCs) or cells derived from other tissues (e.g., endothelium or placenta), have shown great promise in treating other nonradiation injuries to and diseases of the bone marrow, skin, gastrointestinal tract, brain, lung and heart. To explore the potential use of these therapies in the treatment of victims after acute radiation exposure, the National Institute of Allergy and Infectious Diseases co-sponsored an international workshop in July, 2015 in Paris, France with the Institut de Radioprotection et de Sûreté Nucléaire. The workshop included discussions of data available from testing in preclinical models of radiation injury to different organs, logistics associated with the practical use of cellular therapies for a mass casualty incident, as well as international regulatory requirements for authorizing such drug products to be legally and readily used in such incidents. This report reviews the data presented, as well as key discussion points from the meeting.

journal_name

Radiat Res

journal_title

Radiation research

authors

DiCarlo AL,Tamarat R,Rios CI,Benderitter M,Czarniecki CW,Allio TC,Macchiarini F,Maidment BW,Jourdain JR

doi

10.1667/RR14810.1

subject

Has Abstract

pub_date

2017-08-01 00:00:00

pages

e54-e75

issue

2

eissn

0033-7587

issn

1938-5404

journal_volume

188

pub_type

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    doi:

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