Researchers at the University of Cambridge have grown functional "mini-lungs" using stems cells derived from the skin cells of patients with a debilitating lung disease. Not only can the development help them in coming up with effective treatments for specific lung diseases like cystic fibrosis, but the process has the potential to be scaled up to screen thousands of new compounds to identify potential new drugs.
Creating miniature organoids has been the focus of many a research group, as it allows scientists to better understand the processes that take place inside an organ, figure out how specific diseases occur and develop or even work towards creating bioengineered lungs.
The research team from the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute studied a lung disease called cystic fibrosis, which is caused by genetic mutation and shortens a patient's average lifespan. Patients have great difficulty breathing as the lungs are overwhelmed by thickened mucus.
To create working mini-lungs, the researchers took skin cells from patients with the most common form of cystic fibrosis and reprogrammed them to an induced pluripotent state (iPS), which allows the cells to grow into a different type of cell inside the body.
They then activated a process called gastrulation which pushes the cells to form distinct layers such as the endoderm and foregut. The cells were then pushed further to form distal airway tissue, the part of the lung that deals with exchange of gases.
“In a sense, what we’ve created are ‘mini-lungs’," says Dr Nick Hannan, the lead researcher. “While they only represent the distal part of lung tissue, they are grown from human cells and so can be more reliable than using traditional animal models, such as mice."
To find out whether the mini lungs could actually be used to screen drugs, the team tested them out with the aid of chloride-sensitive fluorescent dye. Cells from cystic fibrosis patients typically malfunction and don't allow the chloride to pass through, so there's no change in fluorescence levels.
The team added a molecule that's currently undergoing clinical trials and noted a change in fluorescence, signaling that it was effective in getting the diseased lung cells to function properly and that the mini lungs could, in principle, be used to test potential new drugs.
"We’re confident this process could be scaled up to enable us to screen tens of thousands of compounds and develop mini-lungs with other diseases such as lung cancer and idiopathic pulmonary fibrosis," says Dr Hannan. "This is far more practical, should provide more reliable data and is also more ethical than using large numbers of mice for such research."
The research was published in the journal Stem Cells and Development.
Source: University of Cambridge