A team of scientists has created a straightforward method for automated production of lung organoids, potentially transforming the development of lung disease treatments. These tiny structures, which contain the same types of cells found in real lungs, could allow for more efficient testing of early-stage experimental drugs without relying on animal models.
In the future, patients might have personalized organoids created from their own tissue to test potential treatments beforehand.
“The key takeaway for now—plain and simple—is that it works,” said Professor Diana Klein from the University of Duisburg-Essen, lead author of the study published in Frontiers in Bioengineering and Biotechnology.
“This demonstrates that, in principle, lung organoids can be generated through an automated process. These intricate structures more accurately mimic the in vivo environment than traditional cell lines, making them an excellent model for studying disease.”
“In the next phase, the organoids could be employed to screen potential therapies using high-throughput approaches,” said Klein.
“Which treatments work, and at what doses? This could speed up the development of targeted medications for patients. Additionally, the organoids might help predict how individual patients will respond to radiotherapy or other treatments.”
Stem Cells Take the Lead
Developing improved treatments for lung diseases could save millions of lives globally. However, the lung’s intricate structure makes it challenging to replicate in the lab for fast and effective testing of therapies. Lung organoids are promising for research, but manual production has been too labor-intensive for preclinical testing.
“You start with a single cell—here, a stem cell—and multiply it; the cells then grow in an appropriate plastic dish,” explained Klein.
Once the cells have multiplied enough, we detach them from the plastic dish and ‘activate’ them to form small cell clusters. This is done by placing a specific number of cells in an anti-adhesive dish, where they float together and form embryoid bodies.
“These clusters are then exposed to different growth factors—compounds normally present in the lungs or during lung development. Under these conditions, the cells differentiate into the various cell types found in the lungs.”
The researchers cultured the embryoid bodies in a stirred tank with nutrient-rich medium. At the same time, they manually cultured a control group of organoids on a standard growth plate.
The organoids were cultured in the tank for four weeks and then examined using microscopy, immunofluorescence, immunohistochemistry, and RNA sequencing to assess their development, cell composition, and similarity to conventionally grown organoids.
The analysis showed that both groups of organoids formed the lung-like structures—airways and alveoli—that researchers aimed for, and RNA sequencing confirmed the presence of characteristic epithelial and mesodermal lung cells.
While both methods produced the same cell types, the proportions differed slightly; manually grown organoids had more alveolar cells, whereas the bioreactor-grown organoids tended to be larger but contained fewer alveolar spheres.
Mini Lungs Boost Research Potential?
The bioreactor’s ability to produce more organoids with less manual effort could revolutionize lung disease research. Further testing is needed to optimize growth conditions and make organoids more lifelike.
“Organoids can’t yet fully reproduce the lung’s cellular composition,” said Klein. “Some elements, like immune cells and blood vessels, are still missing. However, the organoids display very accurate bronchiolar and alveolar structures. We don’t have blood flow, so the environment is relatively static.
“For patient-focused screening, these organoids can still reveal how cells respond to treatments.” While not as complex as a whole organism, they are human-based and contain the same cell types found in patients.
“There’s still plenty of room for improvement,” Klein added. “We need reliable, scalable methods for producing organoids on a large scale. This involves careful planning of the bioreactor design, selecting the right cell types, and fine-tuning the cultivation conditions. But we’re actively working on it.”
Read the original article on: Medical Xpress
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