As astronauts venture further into space, their exposure to harmful radiation rises. Researchers from Columbia University are simulating the effects of space radiation here on Earth to determine its impact on human physiology using multi-organ tissue chips. Their work documents the differential effects seen in tissues after acute and prolonged radiation exposure and identifies multiple genes of interest that could help inform the development of future radioprotective agents.

Their study appears in Advanced Science.

“As deep space exploration continues to unfold, it is vital to understand the physiological damage caused by space radiation to better mitigate its effects. By exposing multi-organ models to simulated cosmic radiation, this study has laid the groundwork to aid in this effort,” commented Jermont Chen, Ph.D., a program director in the Division of Discovery Science and Technology at NIBIB.

During space travel, astronauts are continuously bombarded with galactic cosmic rays (GCRs), which are composed of fast-moving atoms traveling at nearly the speed of light. Due to their high speed, the electrons of these atoms have been stripped away, leaving behind ionized nuclei that knock off electrons into the surrounding material they pass through like a wrecking ball. On Earth, we are protected from radiation sources like GCRs by the planet’s atmosphere and magnetic field that act as a shield against radiation.

“GCRs are much more damaging than either gamma rays or X-rays due to the heavy ions that can interact with spacecrafts and release high-energy secondary particles, which can damage astronauts’ DNA in tissues throughout the body. Exposure to GCRs is predicted to increase the risks of developing acute radiation syndrome and may have other health consequences, including cancer and heart disease,” explained lead study author Naveed Tavakol, Ph.D., a postdoctoral research scientist in Columbia University’s Department of Biomedical Engineering.

Current models to study GCR damage come with significant caveats. Preclinical animal models don’t fully mimic the nature of human biology and cannot accurately represent factors specific to each patient, like ethnicity and age. Additionally, isolated human cell models lack the architectural and functional maturity of human tissues when studied outside the body, explained Tavakol.

Cue the multi-organ-on-a-chip (multi-OOC), a more accurate representation of individual human physiology. Already developed at Columbia University, this plug-and-play system allows for patient-specific tissue models of different organs to be interconnected by vascular flow, as they are in the human body. This system allows for each tissue type to be grown in its optimal environment while also supporting the vital communication and migration of immune cells between organs.

Using a multi-OOC composed of bone marrow, cardiac muscle, and liver tissue, this team of bioengineers sought to understand the effects of radiation exposure on organ function and gene expression. Astronauts are exposed to both acute radiation (short, but intense exposure like during space walks) and prolonged radiation (like during extended stays on the International Space Station). The researchers used their technology to quantify the impact of both types of exposure and compared them to a control model that was not exposed to radiation.

Working with The Center for Radiological Research at Columbia and Columbia’s off-campus Nevis Laboratory facility, Tavakol and team subjected their multi-OOCs to radiation using an accelerator-based neutron irradiator system. This accelerator produces high-energy neutrons by accelerating hydrogen and deuterium ions and bombarding them into a stiff metal known as beryllium. The neutrons produced from these collisions closely resemble the ionized nuclei found in GCR. Multi-OOCs were exposed to a prescribed radiation dose of 0.5 gray in either an acute fashion (delivered over 15-20 minutes) or in a protracted fashion (0.04 gray, 12 times a day for three minutes over two weeks).

“We found that the same cumulative dose of radiation over a period of two weeks, as opposed to a single acute dose, resulted in a greater effect on the functions of bone marrow and heart muscle,” noted Tavakol. He explained that protracted radiation was seen to increase the differentiation of bone marrow stem cells into immune cells and to decrease their differentiation into blood cells, a potential precursor to anemia and/or blood cancers.

Additionally, changes in the ability of cardiac cells to contract were seen after protracted radiation, and are potentially predictive of hypertrophic cardiomyopathy, wherein the heart muscle becomes too thick and stiff to effectively pump blood. Tavakol added that genetic sequencing of immune cells that had migrated to the circulating compartment revealed 58 genes specifically affected by protracted radiation, identifying potential radioprotective targets to explore.

“These findings identify a suite of biomarkers that may help the development of future radiation countermeasures and prove the feasibility and scale-up potential of the multi-OOCs to study the body’s response to deep space travel,” said Gordana Vunjak-Novakovic, Ph.D., University Professor and director of the Tissue Engineering Resource Center at Columbia.

“Further, this study sets the stage for the establishment of individualized ‘astronaut on chip’ platforms that may give insight into astronaut-specific responses to radiation and radiation countermeasures.”