Scientists at the University of Adelaide have shown that it is possible to use stem cells to replace defective cells in the airways of mice with cystic fibrosis, offering hope of a cure for cystic fibrosis in humans. The transplanted stem cells were able to pass on healthy genes to daughter cells and replenished airway cells.
Cystic fibrosis is a genetic disorder caused by mutations of both copies of the gene for cystic fibrosis transmembrane conductance regulator (CFTR) protein, which is involved in the production of mucus, digestive fluids, and sweat. Without functional CFTR protein, mucus is thin instead of thick and fails to function correctly.
A mutation in one copy of the CFTR gene means an individual is a carrier of the disease. If both parents are carriers there is a one in four chance that a baby will be born with the disease. One in 25 people carry the defective gene and cystic fibrosis affects around 70,000 people worldwide. There is currently no cure for cystic fibrosis, only treatments that can manage the symptoms of the disease and slow its progression. Even with treatment, the disease causes a significant shortening of life span.
The researchers have previously attempted to transplant stem cells into mouse airways, although engraftment was inefficient. This lead the researchers to develop a new technique in which they disrupted the epithelial cell layer using polidocanol (PDOC), removing the existing surface cells in the airway and then creating the necessary space to introduce the stem cells.
“This study provides proof-of-principle that transplantation of healthy cells in the airways is feasible with the potential to alleviate CF-related airway disease and other airway diseases such as primary ciliary dyskinesia,” wrote the researchers.
To avoid rejection stem cells would need to be harvested from patients, genetically modified, and then reintroduced.
While the research can be seen as a major breakthrough, the technique will need to be further refined but the researchers suggest that it should be possible to use the technique to return cystic fibrosis patients’ airways to near normal or at least halt the progression of the disease. It could also prevent the onset of lung disease in young patients with the double mutation.
The study is detailed in the paper – Epithelial disruption: a new paradigm enabling human airway stem cell transplantation – which was published in the journal Stem Cell Research & Therapy on June 13, 2018. DOI: 10.1186/s13287-018-0911-4