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Updated: Dec 24, 2025
Monitoring Cancer Cell Invasion and T-Cell Cytotoxicity in 3D Culture
Published on: June 23, 2020
Evaluation of Bystander Infection of Oncolytic Virus using a Medium Flow Integrated 3D In Vitro Microphysiological
Sang Woo Lee1, Kyoung Jin Lee2,3, Soo Yeon Jeong1
1Biomedical Engineering Research Center, Asan Institute for Life Science, Asan Medical Center, Seoul, 05505, Korea.
Abstract:
Replicable oncolytic viruses (OVs) induce tumor cell lysis and release viral progeny. The released progeny virions and cell debris can spread within surrounding tumor cells or blood vessels. These released molecules may also induce bystander damage in additional tumor cells through spreading within surrounding tumor cells or blood vessels. However, this effect has not been clearly demonstrated due to the difficulty of direct observation. Here, the bystander infection of OVs by vessel delivery and selective infection in 3D multicellular tumoroids (MCTs) in an in vitro microphysiological system (MPS) with integrated medium flow is demonstrated. This study uses replicable vesicular stomatitis virus (VSV)-green fluorescence protein (GFP) to identify the location of infection in 3D MCTs. Using this MPS, the oncoselective infection by VSV-GFP and the spreading by delivery of OVs through flow via block-to-block linkage of the primary infected MPS with uninfected 3D MCTs in an integrated MPS is observed. This MPS enables real-time monitoring and various analysis for the bystander infection of OVs. It is expected that the 3D in vitro MPS can be suitable to investigate the oncoselective spreading and bystander infection of OVs.
Insights
Oncolytic viruses (OVs) were studied for their ability to infect tumor cells and spread. A new 3D in vitro model demonstrated how OVs spread and cause bystander infection in tumors.
Area of Science:
- Oncology
- Virology
- Biotechnology
Background:
- Oncolytic viruses (OVs) lyse tumor cells, releasing progeny to infect more cells.
- Direct observation of OV bystander infection in tumors is challenging.
- Existing models lack the complexity to study OV spread and infection dynamics.
Purpose of the Study:
- To demonstrate bystander infection of OVs via vessel delivery in a 3D multicellular tumoroid (MCT) model.
- To utilize a microphysiological system (MPS) for real-time monitoring of OV infection and spread.
- To investigate the oncoselective infection and spreading of OVs in a controlled in vitro environment.
Main Methods:
- Development of a 3D in vitro microphysiological system (MPS) with integrated medium flow.
- Use of replicable vesicular stomatitis virus-green fluorescence protein (VSV-GFP) to track infection.
- Block-to-block linkage of infected and uninfected MCTs within the MPS to observe viral spread.
Main Results:
- Demonstrated bystander infection of OVs through vessel delivery in 3D MCTs.
- Observed oncoselective infection by VSV-GFP within the MPS.
- Successfully visualized OV spreading via medium flow between linked tumoroid blocks.
Conclusions:
- The 3D in vitro MPS effectively demonstrates OV bystander infection and oncoselective spreading.
- This MPS allows for real-time monitoring and analysis of OV dynamics.
- The developed system is suitable for investigating OV efficacy and mechanisms in a tumor microenvironment.
