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Published on: January 10, 2025
Microfluidic Coculture Device for Monitoring of Inflammation-Induced Myocardial Injury Dynamics
Xiaoni Ai1, Wenbo Lu1, Kewu Zeng1
1State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences , Peking University , Beijing 100191 , China.
Abstract:
Emerging awareness of cardiac macrophages' role in inflammation after myocardial infarction indicates that overabundant proinflammatory macrophages induce accentuated myocardial injury. The investigation of the macrophages-cardiomyocytes interaction and inflammation-induced dynamic damage in myocardial infarction, especially in a spatiotemporally controlled manner, remains a huge challenge. Here, we developed an in vitro model using a microfluidic coculture system to mimic inflammatory cardiac injury. To our knowledge, on-chip pathological models focused on inflammation-induced myocardial injury have not been reported. The device consists of two sets of thin interconnecting grooves that isolate heterogeneous cells spatially but maintain their soluble factors communication. The mass transportation is visually characterized, and the complete diffusion reaches equilibrium within 100 s. We investigate the dynamic interaction between the macrophages and the cardiomyocytes in the spatiotemporal controlled microenvironment, mimicking a key aspect of the in vivo pathophysiological process. The results show that the activated macrophages induce time-lapsed apoptotic responses of the cardiac cells and damage mitochondria membrane integrity. The anti-inflammatory and cardio-protective effects of quercetin were explored on the chip. The extent of caspase-3 activation is asynchronous in the individual cardiac cells, suggesting the different apoptosis dynamics. We further demonstrate that the mechanism of activated inflammation is associated with the upregulation of several inflammatory cytokines and NF-κB pathway. Thus, the developed microfluidic coculture device provides a useful tool for real-time monitoring of inflammatory response for myocardial disease and holds potential for anti-inflammatory drug screening.
Insights
A novel microfluidic model reveals how inflammatory macrophages damage heart cells after myocardial infarction. This tool aids in studying heart inflammation and screening anti-inflammatory drugs like quercetin.
Area of Science:
- Biomedical Engineering
- Cardiovascular Research
- Cell Biology
Background:
- Cardiac macrophages are increasingly recognized for their role in myocardial infarction (MI) inflammation.
- Proinflammatory macrophages can exacerbate myocardial injury post-MI, but their dynamic interaction with cardiomyocytes is poorly understood.
- Investigating inflammation-induced damage in MI requires spatiotemporally controlled models.
Purpose of the Study:
- To develop an in vitro microfluidic coculture system to model inflammation-induced cardiac injury.
- To investigate the spatiotemporal dynamics of macrophage-cardiomyocyte interactions in an inflammatory setting.
- To explore the therapeutic potential of quercetin in mitigating inflammation-induced cardiac damage.
Main Methods:
- A microfluidic device with interconnected grooves was designed to spatially isolate, yet allow communication between, macrophages and cardiomyocytes.
- The device facilitated controlled mass transport and diffusion, reaching equilibrium within 100 seconds.
- Real-time monitoring of cellular responses, including apoptosis and mitochondrial integrity, was performed.
Main Results:
- Activated macrophages induced time-lapse apoptotic responses and mitochondrial damage in cardiac cells.
- Caspase-3 activation was asynchronous, indicating varied apoptosis dynamics among individual cardiac cells.
- The inflammatory mechanism involved upregulation of inflammatory cytokines and the NF-κB pathway.
- Quercetin demonstrated anti-inflammatory and cardioprotective effects within the microfluidic model.
Conclusions:
- The developed microfluidic coculture system effectively mimics inflammatory cardiac injury, offering a novel platform for studying macrophage-cardiomyocyte interactions.
- This model provides a tool for real-time monitoring of inflammatory responses in myocardial disease.
- The system holds potential for high-throughput screening of anti-inflammatory drugs for cardiovascular conditions.
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