A team of researchers has developed an automated manufacturing process for lung organoids, which may significantly enhance the testing of cancer treatments. These miniature lung structures mimic the cellular composition of actual lungs, paving the way for advanced drug testing without the need for animal models. The breakthrough could lead to personalized medicine, allowing patients to have organoids created from their own tissue to evaluate potential treatments before they are administered.
Professor Diana Klein of the University of Duisburg-Essen led the study, which was published in the journal Frontiers in Bioengineering and Biotechnology. She stated, “The best result for now—quite simply—is that it works. This means that, in principle, lung organoids can be produced using an automated process.” The ability to create these complex structures more efficiently could revolutionize research in lung diseases.
Advancements in Drug Testing
Current methods for developing lung organoids require extensive manual labor, limiting their use in preclinical testing. The new automated process enhances efficiency and scalability, enabling researchers to produce larger quantities. This advancement could accelerate the development of specific medications tailored to individual patients.
Klein explained the procedure: “You take a starting cell, in our case, a stem cell, and multiply it—the cells grow in a suitable plastic dish. Once the cells have grown sufficiently, you then detach them from the plastic dish and ‘animate’ the cells to form small cellular aggregates.” These aggregates are then placed in an anti-adhesive dish, promoting the formation of embryoid bodies, which can develop into various lung cell types when treated with specific growth factors.
The organoids are then cultivated in a specialized bioreactor that allows for continuous stirring and optimal growth conditions. After four weeks, both the bioreactor-grown organoids and a control set were analyzed using various scientific techniques to compare their development and cellular composition.
Analysis confirmed that both sets developed structures resembling airways and alveoli, essential components of the lung. RNA sequencing revealed that they produced the characteristic epithelial and mesodermal cells found in lung tissue, although the proportions differed slightly. The organoids created in the bioreactor were larger but had fewer alveolar spheres compared to those grown using traditional methods.
Future Directions and Potential
The ability to manufacture lung organoids in bulk could transform lung disease research, potentially saving millions of lives globally. Despite the progress, Klein noted that further optimization is necessary to improve the organoids’ ability to replicate real-life lung conditions. “Organoids can’t yet fully recapitulate the lung cellular composition. Some cells are still missing from the ‘big picture,’ such as infiltrating immune cells and blood vessels,” she said.
The researchers are committed to refining their methods to enhance the organoids’ complexity and functionality. “There is still a lot of room for optimization. We need robust and scalable protocols for large-scale organoid production,” added Klein. This ongoing work will focus on refining bioreactor design, cell types, and cultivation conditions.
With continued advancements, lung organoids could serve as a vital platform for patient-specific drug screening, offering critical insights into how individual patients might respond to various treatments. The research marks a significant step toward more effective therapies for lung diseases, opening new avenues for personalized medicine.
For more details, refer to the study titled “Upscaling: Efficient generation of human lung organoids from induced pluripotent stem cells using a stirring bioreactor,” published on March 15, 2024.
