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

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.

Radiotherapy on-chip: microfluidics for translational radiation oncology

“…Other groups designed microfluidic chips to investigate the interplay between 3D-microvasculature and biological response to radiation, illustrating the broad capacity of microfluidics for this field. 127 Indeed, Guo et al introduced a microvasculature-on-chip model, irradiated it with a 6 MV X-ray beam from a linear accelerator, and showed its superiority over 2D microvasculature by measuring apoptosis, radiation effects on tight junctions, and DNA damage and repair. 76 Additionally, Yi et al designed a glioblastoma-on-chip emulating various organotypic aspects of glioblastoma, including the native-like extracellular matrix, oxygen gradient, and cancer-stroma organization (Fig.…”

The Effect of Irradiation on the Skin upon Breast Cancer Radiotherapy Studied by FTIR Spectroscopy

“…and the reductant species hydrated electrons (eaq -) and hydrogen atoms, which by the indirect interactions with biological molecules, provoking changes of the redox potential and increasing the radiation-induced damage [2,5]. Skin models have been used to study the effects induced by ionizing radiations in vitro [6]. It has been shown that irradiation affects epidermal homeostasis by compromising the regulatory mechanism that balances proliferation and cell loss [7].…”