Three-dimensional clysters of cells that act just like a pair of mini lungs have been developed by scientists in the UK, using stem cells take from patients with cystic fibrosis (CF). They're now using them to test new kinds of drugs to combat this disease - of which one in 25 people are carriers.
"In a sense, what we've created are 'mini-lungs'," lead researcher, Nick Hannan from the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute at the University of Cambridge, said in a press release. "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. We can use them to learn more about key aspects of serious diseases – in our case, cystic fibrosis."
Cystic fibrosis is the most common genetically acquired, life-shortening chronic illness in Australia, and in the US and Europe, affects around one in every 3,500 births. On average, one in 25 people carry the CF gene - most of whom won't ever know it. If a child is conceived by two carriers, there's a 25 percent chance it will be born with the disease; a 50 percent chance that it will be a carrier; and a 25 percent chance that it will be a non-carrier.
The disease is caused by a single genetic mutation, but this type of mutation can differ between patients. It progresses when the lungs become filled with a dense mucus, which makes it difficult for a patient to breath, and can increase the risk of respiratory infection. People affected by CF tend to have a shorter than average lifespan because of this.
In order to more safely and effectively trial new types of drugs and treatment for the disease, the team extracted skin cells from patients with the most common CF-causing genetic mutation, called the delta-F508 mutation. This mutation causes a protein called CFTR to fold in weird shapes, which stalls the movement of chloride, and therefore water, in and out of the lung tissue cells. This causes the mucus build-up and long-term bacterial infections, which scars the lung tissue.
Using these lung skin cells, the team induced a pluripotent state, which reverts them into stem cells that can be programmed to grow into any type of cell that's needed. From these, the team cultivated embryonic lung cells by activating a process called gastrulation. The team explains the process in a press release:
"The cells form distinct layers including the endoderm and then the foregut, from which the lung 'grows', and then pushes these cells further to develop into distal airway tissue. The distal airway is the part of the lung responsible for gas exchange and is often implicated in disease, such as cystic fibrosis, some forms of lung cancer and emphysema."
The team has published the results in Stem Cells and Development.
"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," said 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."