Revolutionizing Heart Research with Microtissues
Tiny heart tissues are changing drug testing and disease studies.
Tessa de Korte, Benjamin B. Johnson, Georgios Kosmidis, Benoit Samson-Couterie, Mervyn P. H. Mol, Ruben W. J. van Helden, Louise François, Viviana Meraviglia, Loukia Yiangou, Tom Kuipers, Hailiang Mei, Milena Bellin, Stefan R. Braam, Shushant Jain, Christine L. Mummery, Richard P. Davis
― 5 min read
Table of Contents
- The Rise of Human Induced Pluripotent Stem Cells
- Maturity Matters: The Need for Adult-like Cells
- Scaling Up: Automation and Efficiency
- Studying Heart Diseases with cMTs
- The Experiment: What Was Done
- The Results Are In: Successful Drug Screening
- The Benefits of Automation
- The Pros and Cons of Microtissues in Drug Discovery
- Conclusion: The Future Looks Bright
- Key Takeaways
- Original Source
Cardiac microtissues (CMTS) are tiny clusters of heart cells, specifically made from induced pluripotent stem cells (iPSCs). These cells are special because they can turn into any type of cell in the body, which makes them quite handy for scientific research. In recent years, these mini heart tissues have become very important for testing new drugs and understanding heart diseases. Why bother with cMTs, you ask? Well, they help scientists see how medicines can affect the heart without needing to test them on actual people first.
The Rise of Human Induced Pluripotent Stem Cells
To grasp the significance of cMTs, we must first look at human induced pluripotent stem cells (HiPSCs). These are regular cells that have been “reprogrammed” to behave like stem cells. Think of them like a Swiss Army knife of cells; they can eventually turn into any kind of cell, including heart cells. This has led to their rise in drug discovery, serving as a more ethical alternative to animal testing. Regulatory bodies like the FDA have even given a nod to these cells for testing drug safety.
Maturity Matters: The Need for Adult-like Cells
While hiPSCs are great, they often behave more like immature heart cells found in a fetus rather than fully mature adult cells. Why is this a problem? Well, if we're trying to understand how adult hearts respond to drugs, having cells that act like babies might not give us the best results. Recent developments in 3D cardiac models have helped create more mature heart cells from hiPSCs, but don’t pop the champagne just yet. These models can require a lot of expertise, specific equipment, and can be as expensive as a fancy dinner out.
Automation and Efficiency
Scaling Up:The good news is that researchers have found ways to produce these cMTs in a more cost-effective and scalable manner. By using techniques that don't require complex setups, scientists can make batches of these tiny heart tissues without breaking the bank. Even better, researchers are looking into robotics to streamline the process. Imagine a robot doing all the heavy lifting-no more late-night lab work.
Studying Heart Diseases with cMTs
One of the diseases researchers are particularly interested in is catecholaminergic polymorphic ventricular tachycardia (CPVT1). This mouthful of a name refers to a genetic condition that can cause the heart to beat irregularly, which isn't exactly a good thing for anyone. By using cMTs made from patients affected by CPVT1, scientists can study how this condition affects heart function and see how different drugs might help.
The Experiment: What Was Done
In a recent series of studies, researchers created cardiac microtissues from various heart cell types. These tiny models were then used to test how well they could replicate heart disease symptoms and respond to various medications. Some cMTs were engineered to carry the CPVT1 mutation. This allowed researchers to accurately observe the arrhythmias-irregular heartbeats-these cells produced.
The Results Are In: Successful Drug Screening
By conducting various tests, scientists were able to see how well the microtissues responded to certain drugs. They found some compounds that could “rescue” the heart cells from the arrhythmias caused by CPVT1. Among the standout drugs was flecainide, a medication previously used to treat arrhythmias in patients.
The Benefits of Automation
One of the major breakthroughs from this research was the use of automation to create and analyze cMTs more efficiently. By employing advanced liquid-handling robots, researchers could produce cMTs quickly and with consistent quality. Imagine a robot whipping up batches of tiny heart cells while scientists sip coffee and take notes-it's like a futuristic lab sci-fi movie come to life!
The Pros and Cons of Microtissues in Drug Discovery
While cMTs offer many advantages, such as being more representative of real heart tissues than other models, they still come with limitations. Researchers sometimes face challenges when trying to mimic every single aspect of a human heart, especially when it comes to drug responses.
Conclusion: The Future Looks Bright
The research into cardiac microtissues is paving the way for better drug testing methods, particularly for heart conditions like CPVT1. Thanks to modern science and a little bit of robotics, the future of drug discovery looks promising. So, the next time you hear about a new heart medication, remember the tiny heroes working quietly in the lab-our friendly neighborhood cardiac microtissues!
Key Takeaways
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Cardiac Microtissues (cMTs): Mini heart tissues derived from hiPSCs that help researchers test drugs and study heart diseases.
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hiPSCs: Special cells that can become any type of cell in the body, making them invaluable for research.
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Maturity Matters: Developing adult-like cells is crucial for accurate drug testing.
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Automation: Robots are being used to streamline the production of cMTs, making the process quicker and more efficient.
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Studying CPVT1: These cMTs are used to better understand and treat arrhythmias associated with the genetic condition CPVT1.
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Drug Screening: Successful tests have shown that some drugs can effectively rescue cMTs from arrhythmic behavior, which is promising for patient treatment.
With further development and optimization, these heart models could soon become a staple in laboratories and hospitals around the world, improving the lives of many who suffer from heart diseases.
Title: Industrialization of three-dimensional hiPSC-cardiac microtissues for high-throughput cardiac safety and drug discovery screening
Abstract: Current cardiac cell models for drug screening often face a trade-off between cellular maturity and achieving high throughput. While three-dimensional human induced pluripotent stem cell-based heart models typically exhibit more adult-like features, their application is hindered by the need for large cell numbers or complex equipment. Here, we developed cost-effective methods to scale up production of three-dimensional cardiac microtissues (cMTs) containing three cardiac cell types, and assess calcium transients and action potential metrics for high-throughput screening (HTS). Automating the procedure revealed reproducible drug responsiveness and predictive accuracy in a reference compound screen. Furthermore, an arrhythmic phenotype was reliably triggered in cMTs containing cardiomyocytes with a RYR2 mutation. A screen of FDA-approved drugs identified 17 drugs that rescued the arrhythmic phenotype. Our findings underscore the scalability of cMTs and their utility in disease modelling and HTS. The advanced "technology-readiness-level" of cMTs supports their regulatory uptake and acceptance within the pharmaceutical industry.
Authors: Tessa de Korte, Benjamin B. Johnson, Georgios Kosmidis, Benoit Samson-Couterie, Mervyn P. H. Mol, Ruben W. J. van Helden, Louise François, Viviana Meraviglia, Loukia Yiangou, Tom Kuipers, Hailiang Mei, Milena Bellin, Stefan R. Braam, Shushant Jain, Christine L. Mummery, Richard P. Davis
Last Update: 2024-12-02 00:00:00
Language: English
Source URL: https://www.biorxiv.org/content/10.1101/2024.11.29.626032
Source PDF: https://www.biorxiv.org/content/10.1101/2024.11.29.626032.full.pdf
Licence: https://creativecommons.org/licenses/by/4.0/
Changes: This summary was created with assistance from AI and may have inaccuracies. For accurate information, please refer to the original source documents linked here.
Thank you to biorxiv for use of its open access interoperability.