Radiation induces acute and subacute vascular regression in a three-dimensional microvasculature model

Dong-Hee Choi; Dongwoo Oh; Kyuhwan Na; Hyunho Kim; Dongjin Choi; Yong Hun Jung; Jinchul Ahn; Jaehoon Kim; Chun-Ho Kim; Seok Chung

doi:10.3389/fonc.2023.1252014

Radiation induces acute and subacute vascular regression in a three-dimensional microvasculature model

Front Oncol. 2023 Oct 16:13:1252014. doi: 10.3389/fonc.2023.1252014. eCollection 2023.

Authors

Dong-Hee Choi^{1

2}, Dongwoo Oh³, Kyuhwan Na^{1

2}, Hyunho Kim^{1

4}, Dongjin Choi⁵, Yong Hun Jung^{1

2}, Jinchul Ahn^{1

2}, Jaehoon Kim^{1

6}, Chun-Ho Kim⁵, Seok Chung^{1

3

7}

Affiliations

¹ School of Mechanical Engineering, Korea University, Seoul, Republic of Korea.
² R&D Research Center, Next&Bio Inc, Seoul, Republic of Korea.
³ Korea University-Korea institute of Science and Technology (KU-KIST) Graduate School of Converging Science and Technology, Korea University, Seoul, Republic of Korea.
⁴ Center for Systems Biology, Massachusetts General Hospital, Boston, MA, United States.
⁵ Laboratory of Tissue Engineering, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea.
⁶ George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, United States.
⁷ Center for Brain Technology, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, Republic of Korea.

Abstract

Radiation treatment is one of the most frequently used therapies in patients with cancer, employed in approximately half of all patients. However, the use of radiation therapy is limited by acute or chronic adverse effects and the failure to consider the tumor microenvironment. Blood vessels substantially contribute to radiation responses in both normal and tumor tissues. The present study employed a three-dimensional (3D) microvasculature-on-a-chip that mimics physiological blood vessels to determine the effect of radiation on blood vessels. This model represents radiation-induced pathophysiological effects on blood vessels in terms of cellular damage and structural and functional changes. DNA double-strand breaks (DSBs), apoptosis, and cell viability indicate cellular damage. Radiation-induced damage leads to a reduction in vascular structures, such as vascular area, branch length, branch number, junction number, and branch diameter; this phenomenon occurs in the mature vascular network and during neovascularization. Additionally, vasculature regression was demonstrated by staining the basement membrane and microfilaments. Radiation exposure could increase the blockage and permeability of the vascular network, indicating that radiation alters the function of blood vessels. Radiation suppressed blood vessel recovery and induced a loss of angiogenic ability, resulting in a network of irradiated vessels that failed to recover, deteriorating gradually. These findings demonstrate that this model is valuable for assessing radiation-induced vascular dysfunction and acute and chronic effects and can potentially improve radiotherapy efficiency.

Keywords: adverse effects; microvasculature-on-a-chip; quantification; radiation treatment; radiation-injured vasculature.

Grants and funding

This work was supported by a Korea Planning & Evaluation Institute of Industrial Technology (KEIT) grant funded by the Korean government (MSIT) (No. 20009125), a National Research Foundation (NRF) grant funded by the Korean government (MSIT) (2022M3A9B6018217), and the Technology Innovation Program (20009853, Establishment of a high-content 3D Organ-on-a-chip system for studying pancreatic disease modeling in vitro) funded by the Ministry of Trade, Industry & Energy (MOTIE, Korea).