Abstract
During radiotherapy, microenvironments neighboring the tumor are also exposed to gamma irradiation; this results in unexpected side effects. Blood vessels can serve as microenvironments for tumors and they play an important role in providing nutrients to tumors. This is mostly related to tumor progression, metastasis, and relapse after therapy. Many studies have been performed to obtain a better understanding of tumor vasculature after radiotherapy with in vitro models. However, compared to 3-D models, 2-D in vitro endothelial monolayers cannot physiologically reflect in vivo blood vessels. We previously remodeled the extracellular matrix (ECM) hydrogel that enhanced the tight barrier formation of 3-D blood vessels and the vascular endothelial growth factor (VEGF) gradient induced angiogenesis in a microfluidic device. In this study, the blood vessel model is further introduced to understand how gamma irradiation affects the endothelial monolayer. After the gamma irradiation exposure, we observed a collapsed endothelial barrier and a reduced angiogenic potential. Changes in the cell behaviors of the tip and stalk cells were also detected in the angiogenesis model after irradiation, which is difficult to observe in 2-D monolayer models. Therefore, the 3-D in vitro blood vessel model can be used to understand radiation-induced endothelial injuries.
Highlights
Radiation treatment, which is known as radiotherapy, has been widely applied to a variety of solid tumors in which it is used to kill the tumor cells directly or reduce the tumor m ass[1,2,3,4]
This study demonstrates that gamma irradiation exposure weakens the barriers of the endothelial cell and it can be visualized through the diffusion of dextran molecules across the endothelial barriers
We used this method to form a 3-D endothelial barrier, and human dermal microvascular endothelial cells (hMVEC) were used because this endothelial cell type displays superior barrier properties in comparison to umbilical vein endothelial cells[34]
Summary
Radiation treatment, which is known as radiotherapy, has been widely applied to a variety of solid tumors in which it is used to kill the tumor cells directly or reduce the tumor m ass[1,2,3,4]. The reorganization and reduction of cell–cell junctions between endothelial cells are major problems because they increase cell permeability and weaken barrier functions[25,26,27] Most of these studies were conducted on 2-D in vitro culture systems, in which the endothelial cells grow as a homogenous monolayer. 3-D endothelial models have the potential to constitute more realistic biochemical and biomechanical microenvironments for blood vessels These models can support diverse endothelial cell behaviors such as angiogenesis, vasculogenesis, and cell invasion. To the best of our knowledge, this is the first study to show how gamma irradiation exposure affects endothelial cell behaviors in the 3-D hydrogel-incorporated blood barrier model
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