Radiobiological Studies of Microvascular Damage through In Vitro Models: A Methodological Perspective

SIMPLE SUMMARY: Ionizing radiation is used as a treatment for cancer, but it also affects the endothelial cells that make up the microvasculature. In-vitro models can be used to study the detrimental effect of irradiation on those cells. This systematic review analyzed the literature models, highlighting the critical components of the production, irradiation, and analysis of radiobiological in-vitro models for microvascular endothelial cell damage. Based on those data, we suggest future directions, including advanced in-vitro models to recapitulate microenvironment features. We pinpoint essential information to be included for the good characterization of the experiments, especially in terms of the dose delivered by ionizing radiation. ABSTRACT: Ionizing radiation (IR) is used in radiotherapy as a treatment to destroy cancer. Such treatment also affects other tissues, resulting in the so-called normal tissue complications. Endothelial cells (ECs) composing the microvasculature have essential roles in the microenvironment’s homeostasis (ME). Thus, detrimental effects induced by irradiation on ECs can influence both the tumor and healthy tissue. In-vitro models can be advantageous to study these phenomena. In this systematic review, we analyzed in-vitro models of ECs subjected to IR. We highlighted the critical issues involved in the production, irradiation, and analysis of such radiobiological in-vitro models to study microvascular endothelial cells damage. For each step, we analyzed common methodologies and critical points required to obtain a reliable model. We identified the generation of a 3D environment for model production and the inclusion of heterogeneous cell populations for a reliable ME recapitulation. Additionally, we highlighted how essential information on the irradiation scheme, crucial to correlate better observed in vitro effects to the clinical scenario, are often neglected in the analyzed studies, limiting the translation of achieved results.