Little is known about the effects of deep space radiation on hematopoietic progenitor cells (bone marrow stem cells that can become any of the following: platelets, white blood cells and red blood cells, among others). Hematopoietic stem cells give rise to both the blood and immune systems, and damage to these cells from space’s high-radiation environment could have grave immediate and long-term consequences. The goal of Dr. Alan M. Gewirtz’s research is to identify and quantify the risks of deep space radiation to these cells and explore potential countermeasures to negate any cellular and molecular damage. One possibility includes preflight harvest and storage of astronaut stem cells as a safe, effective and relatively inexpensive mechanism for countering long-term damage to cells of the blood-forming systems.
Overview
Effect of Deep-Space Radiation on Human Hematopoietic Stem and Progenitor Cell Function
Principal Investigator:
Alan M. Gewirtz, M.D.
Organization:
University of Pennsylvania School of Medicine
Technical Summary
Original Aims
During the previous funding period, we worked closely with Dr. Betsy Sutherland at Brookhaven National Laboratory to develop a radiation exposure model that is more relevant to the types of radiation flight crews will be exposed to during longer-duration lunar and Mars missions. In this regard, we have carried out low-dose, multi-dose, and mixed-particle exposure of normal human hematopoietic cells to hydrogen and iron, the main constituents of galactic cosmic rays and solar particle events. The Gewirtz Lab tested the functional consequences of such exposure on progenitor and stem cell function in vitro and in xenograft studies employing NOD-SCID mice. The Sutherland Lab examined effects on DNA repair pathways. Both labs examined the effects of shielding, as well as free radical scavengers in their respective experimental systems. In brief, we found that very low doses of either particle are tolerated but that mixed particles are much more damaging. Of note, shielding and radioprotectants appear to be able to ameliorate damage. The data supporting these statements may be found in the more detailed progress report.
- Investigate the cellular consequences of exposing human hematopoietic stem cells (HSC) and progenitor (HPC) cells to an environment which simulates the radiation environment of deep space;
- Examine the molecular consequences of exposing human HSC to an environment which simulates the radiation environment of deep space; and
- Design potential countermeasures to obviate or negate cellular and molecular damage discerned during the course of carrying out Aims 1 and 2.
During the previous funding period, we worked closely with Dr. Betsy Sutherland at Brookhaven National Laboratory to develop a radiation exposure model that is more relevant to the types of radiation flight crews will be exposed to during longer-duration lunar and Mars missions. In this regard, we have carried out low-dose, multi-dose, and mixed-particle exposure of normal human hematopoietic cells to hydrogen and iron, the main constituents of galactic cosmic rays and solar particle events. The Gewirtz Lab tested the functional consequences of such exposure on progenitor and stem cell function in vitro and in xenograft studies employing NOD-SCID mice. The Sutherland Lab examined effects on DNA repair pathways. Both labs examined the effects of shielding, as well as free radical scavengers in their respective experimental systems. In brief, we found that very low doses of either particle are tolerated but that mixed particles are much more damaging. Of note, shielding and radioprotectants appear to be able to ameliorate damage. The data supporting these statements may be found in the more detailed progress report.
Impact
We continued to refine our conceptual model of radiation exposure to human hematopoietic cells and to make it as realistic as possible given the constraints of the cell system we are employing (normal primary cells) and the availability of the radiation as supplied by the NASA Space Radiation Laboratory. We believe the results we generated using the model available are important and support the concern that radiation exposures during extravehicular activity or solar particle event may be damaging.
Earth Applications
The development of effective radiation countermeasures could have significant impact on Earth for civilians and military personnel. With regard to the civilian population, it is quite conceivable that results we obtain will be relevant to patients undergoing cancer chemotherapy and radiation therapy. In this regard, it is possible that our studies will provide reagents and strategies for helping to protect normal tissues from the collateral damage of anticancer treatments. It is also possible that results we generate will be relevant to radiation workers and members of the armed forces who may be exposed to radiation during the course of carrying out their respective duties.
This project's funding ended in 2008