4.7 Article

Gamma irradiation exposure for collapsed cell junctions and reduced angiogenesis of 3-D in vitro blood vessels

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SCIENTIFIC REPORTS
卷 11, 期 1, 页码 -

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NATURE PORTFOLIO
DOI: 10.1038/s41598-021-97692-8

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资金

  1. Korea Evaluation Institute of Industrial Technology (KEIT) - Korea government (MSIT) [20009125]
  2. National Research Foundation of Korea (NRF) - Korea government (MSIT) [2020R1A2B5B03002005]
  3. Ministry of Trade, Industry & Energy (MOTIE, Korea) [20009853]
  4. KIST Institutional Program [2E29200-19-004]
  5. Korea Evaluation Institute of Industrial Technology (KEIT) [20009853, 20009125] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
  6. National Research Foundation of Korea [2020R1A2B5B03002005] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)

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During radiotherapy, surrounding microenvironments of tumor are exposed to gamma irradiation, impacting blood vessels and their role in tumor nutrition. 3-D models show more accurate effects of radiation on endothelial cells compared to 2-D models, providing insight into radiation-induced endothelial injuries.
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.

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