Human Intestinal Organoids and Microphysiological Systems for Modeling Radiotoxicity and Assessing Radioprotective Agents

Abstract

Radiotherapy is a commonly employed treatment for colorectal cancer, yet its radiotoxicity-related impact on healthy tissues raises significant health concerns. This highlights the need to use radioprotective agents to mitigate these side effects. This review presents the current landscape of human translational radiobiology, outlining the limitations of existing models and proposing engineering solutions. We delve into radiotherapy principles, encompassing mechanisms of radiation-induced cell death and its influence on normal and cancerous colorectal cells. Furthermore, we explore the engineering aspects of microphysiological systems to represent radiotherapy-induced gastrointestinal toxicity and how to include the gut microbiota to study its role in treatment failure and success. This review ultimately highlights the main challenges and future pathways in translational research for pelvic radiotherapy-induced toxicity. This is achieved by developing a humanized in vitro model that mimics radiotherapy treatment conditions. An in vitro model should provide in-depth analyses of host-gut microbiota interactions and a deeper understanding of the underlying biological mechanisms of radioprotective food supplements. Additionally, it would be of great value if these models could produce high-throughput data using patient-derived samples to address the lack of human representability to complete clinical trials and improve patients’ quality of life.

Butyrate as a promising therapeutic target in cancer: From pathogenesis to clinic (Review)

“…Butyrate significantly enhanced radiation-induced cell death and enhanced treatment effects compared with administration of radiation alone. Notably, butyrate did not increase radiation-induced cell death and improved regeneration capacity after irradiation in normal organoids ( 155 , 156 ). Butyrate can increase the uptake of serotonin by mouse ileal organoids and alleviate gastrointestinal reactions by providing energy to cancer patients given radiation therapy ( 157 ).…”