Relative biological effectiveness and neural stem cell fate in carbon ion–irradiated human brain organoids

The article investigates how carbon ion radiation affects human neural tissue using brain organoids derived from pluripotent stem cells. Carbon ion therapy, increasingly used in advanced radiotherapy, is known for its high linear energy transfer (LET) and greater relative biological effectiveness (RBE) compared with conventional photon radiation. However, its impact on developing human neural stem cells (NSCs) remains insufficiently understood.

Using three-dimensional human brain organoids as a model, the researchers exposed neural tissue to carbon ion radiation and compared the biological effects with those induced by X-rays. They evaluated DNA damage responses, cell survival, apoptosis, and changes in neural stem cell differentiation. The study found that carbon ion irradiation produced more complex and persistent DNA double-strand breaks than photon irradiation, leading to higher RBE values. This enhanced damage significantly reduced the proliferation capacity of NSCs and altered their differentiation patterns. In particular, irradiated organoids showed decreased stem cell maintenance and a shift toward premature neuronal differentiation, along with increased cell death in progenitor populations.

The findings demonstrate that carbon ions exert stronger biological effects on human neural tissue than conventional radiation, particularly by disrupting neural stem cell fate decisions. These results have important implications for both cancer therapy and radiation risk assessment, especially in pediatric patients or in cases where healthy brain tissue may be exposed. In conclusion, the study highlights the need to carefully balance the therapeutic advantages of carbon ion therapy with potential long-term effects on neural development and regeneration.

Published by Radiotherapy and Oncology 214 (2026) 111224.
DOI: 10.1016/j.radonc.2025.111224