Organoid’s Potential to Advance Low Dose Research
By Loza Taye | April 4th, 2025
Radiation exposure is a constant and unavoidable aspect of life that stems from natural and man-made sources. Background radiation comes from cosmic rays, radon gas, terrestrial radiation, and trace amounts of radioactive isotopes in food and water. Medical procedures such as X-rays, radiation therapy, and occupational environments in healthcare, aviation, and nuclear energy sectors contribute to additional exposure. Although it is known that high doses of radiation can cause detrimental health effects, the risks associated with long-term, low-dose exposure is less understood. A deeper understanding of these effects is crucial for informing effective public health policy. Organoids are a promising model for investigating these effects.
Several factors complicate research on low-dose radiation (LDR). Epidemiological studies, which analyze health outcomes in populations exposed to varying levels of radiation, provide valuable data but are disproportionately conducted on groups exposed to high-dose radiation. Another challenge being the long latency period associated with radiation-induced diseases, particularly cancer. Many radiation-related health effects do not appear until years or decades after exposure, making it difficult to establish direct causal relationships. Additionally, ethical considerations and the long duration of radiation studies further complicate research efforts. While helpful in studying radiation at the molecular level, traditional two-dimensional cell cultures lack the complexity of human tissues. They cannot fully replicate the interactions between different cell types within an organ. Given these limitations, there is a need for more advanced models that can provide accurate and reproducible data on how human tissues respond to low-dose radiation. Organoids represent a promising solution to these challenges, offering a way to study radiation effects in a system that closely resembles human organs.
Organoids are three-dimensional structures derived from stem cells that can self-organize into miniature versions of human organs. These models retain key structural and functional characteristics of their corresponding tissues, allowing researchers to study cellular responses in a more physiologically relevant context than traditional two-dimensional cell cultures. Organoids have been developed for various human tissues— including the brain, intestines, liver, lungs, and kidneys— and provide a platform for studying how different organs respond to radiation exposure.
One of the primary applications of organoids in radiation research is the study of DNA damage and repair mechanisms. Ionizing radiation can cause DNA strands to break, which can lead to mutations and negative long-term health effects. By exposing organoids to low-dose radiation, researchers can analyze how cells detect and repair DNA damage, which genes and molecular pathways are involved, and whether different cell types within an organ exhibit varying sensitivities to radiation. This information is valuable for understanding the risks associated with low-dose radiation exposure and developing strategies to minimize potential harm. Organoids also offer a valuable platform for drug testing and radioprotective research. Everyone's response to radiation is unique, influenced by factors such as genetic variation, age, and overall health. Organoids offer a potential avenue for personalized medicine in the context of radiation exposure. By deriving organoids from patient-specific stem cells, researchers can create models that mimic an individual's unique biology, including their response to radiation. These patient-specific organoids could be used to test various radioactive countermeasures to identify the most effective treatments for that individual. This approach could be particularly valuable for patients undergoing radiation therapy for cancer, as it would allow for the selection of personalized treatments that minimize side effects while maximizing therapeutic efficacy.
One of the key advantages of organoids is their ability to model human-specific responses to radiation in a way that traditional animal models cannot fully replicate. Because organoids are derived from human cells, they provide a more relevant biological context for studying radiation effects. They also allow for greater experimental control, enabling researchers to precisely manipulate radiation dose, exposure duration, and environmental conditions to study specific biological responses. Another advantage is that organoids can be maintained in culture for extended periods, allowing for long-term studies of radiation effects. Organoids also enable high-throughput screening, allowing researchers to simultaneously test multiple conditions or potential protective compounds. From an ethical standpoint, while animal studies remain important for certain aspects of radiation research, the use of human-derived organoids helps bridge the gap between preclinical findings and human health outcomes without the ethical concerns associated with human or animal exposure studies.
With ongoing advancements in this field, organoids will have an increasingly important role in shaping our understanding of radiation biology and in the development of policies and medical practices concerning radiation exposure. The application of organoids in radiation research represents a significant step towards developing safer and more effective strategies for managing low-dose radiation risks.
The views expressed do not necessarily reflect the official policy or position of Johns Hopkins University or Johns Hopkins Bloomberg School of Public Health.
