In vitro and in vivo assessment of direct effects of simulated solar and galactic cosmic radiation on human hematopoietic stem/progenitor cells

Abstract

Future deep space missions to Mars and near-Earth asteroids will expose astronauts to chronic solar energetic particles (SEP) and galactic cosmic ray (GCR) radiation, and likely one or more solar particle events (SPEs). Given the inherent radiosensitivity of hematopoietic cells and short latency period of leukemias, space radiation-induced hematopoietic damage poses a particular threat to astronauts on extended missions. We show that exposing human hematopoietic stem/progenitor cells (HSC) to extended mission-relevant doses of accelerated high-energy protons and iron ions leads to the following: (1) introduces mutations that are frequently located within genes involved in hematopoiesis and are distinct from those induced by γ-radiation; (2) markedly reduces in vitro colony formation; (3) markedly alters engraftment and lineage commitment in vivo; and (4) leads to the development, in vivo, of what appears to be T-ALL. Sequential exposure to protons and iron ions (as typically occurs in deep space) proved far more deleterious to HSC genome integrity and function than either particle species alone. Our results represent a critical step for more accurately estimating risks to the human hematopoietic system from space radiation, identifying and better defining molecular mechanisms by which space radiation impairs hematopoiesis and induces leukemogenesis, as well as for developing appropriately targeted countermeasures.

Effects of High- and Low-LET Radiation on Human Hematopoietic System Reconstituted in Immunodeficient Mice

“…In that respect, two other studies that investigated the effects of radiation on engrafted human hematopoietic system in humanized mice, support some of our conclusions. In one of the studies, humanized mice were used to investigate the effect of space mission-relevant doses of high-LET radiation on human hematopoietic cell reconstitution (48). For this study, human CD34 + cells were irradiated in vitro with 1 Gy of 50 MeV protons, 20 cGy of 1 GeV/n 56 Fe ions, 1 Gy of 137 Cs gamma radiation and a combination of both 56 Fe ions and gamma radiation.…”

Medicina humana espacial: Performance fisiológico y contramedidas para mejorar la salud del astronauta

“…La exposición a SEP, GCR y a uno o más SPE, influyen directamente en la hematopoyesis, es decir, impiden el desarrollo normal de las células progenitoras de la sangre e inducen la génesis de leucemia (67) , incluso al desarrollo de enfermedades trombóticas (68) . En fases iniciales de exposición a la microgravedad y después de una rápida redistribución de líquidos se produce una disminución en el volumen plasmático y un aumento del hematocrito, esta rápida concentración de eritrocitos inhibe a la eritropoyetina y se reduce la masa de los glóbulos rojos, este proceso se denomina hemólisis selectiva lo que se conoce como anemia espacial (69,70) , que ocurre posiblemente por una reducción del factor inducible por hipoxia (HIF-1α) y la expresión de Bcl-2 que es una proteína antiapoptótica alterada en condiciones ambientales espaciales.…”

“…Autores mencionan que la exposición a microgravedad y especialmente la radiación repercuten negativamente en la hematopoyesis y linfopoyesis (67,74) , esta última alteración está asociada a infecciones por parte del microbiota existente en la piel, mucosa e intestinos (76) . En consecuencia, aumenta la proliferación bacteriana, micótica e incluso los virus como el VHS, VEB y VVZ se reactivan (78) .…”

Mission to Mars: Radiation Safety or Radiation Disaster? Space Transit and Mars Radiation Exposure Risks – The Potential Shielding Effect of an Intravehicular Graphene Space Suit and a Storm Shelter During Space Travel

“…Simulation of this environment is being performed at the NASA Space Radiation Laboratory in order to perform radiobiological experiments. A study with simulated high energy protons and Fe ions induced mutations distinct from gamma-rays and resulted in in-vivo development of T-cell acute lymphoblastic leukaemia in mice (9). Interesting human data has emerged from NASA's "Twin Study" showing a change in telomere length, DNA methylation in immune cells along with cognitive and cardiovascular effects during prolonged human spaceflight (10).…”