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.

Combining spatially fractionated radiation therapy (SFRT) and immunotherapy opens new rays of hope for enhancing therapeutic ratio

“…Total doses above 45 Gy can damage tumor microvessels, while doses up to 40 Gy tend to have inconsistent effects on microvasculature. [25] , [26] , [27] , [28] , [29] , [30] , [31] Garcia-Barros et al in a recent communication have postulated that “high dose” radiation of 15 Gy causes an environment of Potential Lethal Damage that makes these cells sensitive to further doses of radiation, especially the endothelial cells of the tumor microvasculature, and this effect is the primary cause of tumor cell death. [32] .…”

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

“…Radiotoxicity of healthy tissues is mediated by a series of interconnected events, while radioresistance in cancer tissues can result in an increase in tumor growth. This can be attributed to a facilitated microenvironment and tumor-enhancing mutations [20][21][22][23].…”

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.…”