Three-dimensional microtissues as an in vitro model for personalized radiation therapy

Area of Science:

• Biomedical Engineering
• Radiation Oncology
• Cell Biology

Background:

• Traditional 2D cell cultures lack the complexity of in vivo environments.
• Animal models present ethical concerns and may not fully replicate human responses.
• There is a need for intermediate models to bridge the gap between 2D and animal studies.

Purpose of the Study:

• To evaluate 3D microtissues as an intermediate model for assessing radiation-induced cellular and DNA damage.
• To investigate the utility of 3D microtissues in the context of personalized radiation therapy.
• To characterize radiation effects on cell viability, metabolic activity, and DNA integrity within 3D microtissues.

Main Methods:

• Generation of 3D microtissues using agarose microwell arrays for controlled size and shape.
• Exposure of 3D microtissues to various doses of X-ray radiation.
• Assessment of cell membrane damage and metabolic activity using MTT and dye inclusion assays.
• Evaluation of DNA damage through micronucleus assay, γ-H2AX immunostaining, and HaloChip assay.

Main Results:

• X-ray radiation exposure led to a reduction in the size of 3D microtissues compared to unexposed controls.
• Radiation was found to retard cell growth within the 3D microtissue structure.
• Outer cells within the microtissues appeared to offer a protective effect for inner cells against radiation damage.

Conclusions:

• 3D microtissues are a viable intermediate model for studying radiation effects.
• This model shows promise for assessing cellular and DNA damage relevant to personalized radiation therapy.
• The 3D microtissue structure influences cellular response to radiation, with potential implications for treatment planning.