Cystic fibrosis, probably best known to us as the illness that appears in the movie and book “Five Feet Apart,” is a disease that affects approximately 40,000 children and adults within the US and around 100,500 people across the globe. This genetic disease affects our body’s cells and proteins—mainly those that create mucus and sweat glands—and causes a disorder that results in many organ failures including the lung, pancreas, and digestive systems. Those who inherit it generally have a much shorter life span than those who do not even after the development of science; they also require at least 2-3 hours a day just for temporary treatments.
Cystic Fibrosis is caused by a mutation of ionocytes, cells that make up 1% of the airway—the rare and newfound ionocytes produce more than 90% of the protein that is diminished in cystic fibrosis, Cystic Fibrosis Transmembrane Regulator (CFTA).
When scientists and researchers figured out what causes the disease, they immediately brought the fact to use. “Maybe we could correct patients’ ionocytes and put them back in the lungs,” said Ruby Wang, a pediatric pulmonologist at Boston Children’s Hospital. Currently, there is not a definitive cure to cystic fibrosis – only a CFTA modulator that often does not work and contains many side effects. In rare instances where it works, the patient has to take the medicine for their entire lifetime without a guarantee that it will continue working. The method of fixing the patient's ionocyte and putting it back into their system might make a revolutionary change to this reality, though it will make the formerly incurable disease remediable.
You may ask, though, how can this extremely rare cell help with such a life-altering disease? To figure this out, Wang and her colleagues tested the theory in an experiment. First, they created induced pluripotent stem cells, which are cells that are able to renew or generate by themself. Then, the team directed the stem cells to differentiate step by step, first generating airway basal-like cells, or iBCs, through using a dual fluorescent reporter system, which allows us to visualize cells at a single-cell level. With this, they tracked developmentally immature lung progenitors (ancestors) and subsequently improved a TP63 program—a gene that provides instructions for making a certain type of protein that helps with cell reproduction and maintenance—during proximal airway epithelial patterning. This resulted in two kinds of lung cells displaying the molecular and functional phenotype airway basal cells, namely NKX2GFP+ and TP63tdTomato+. iBCs and their differentiated offspring forms or creates disorders that characterize acquired and genetic airway diseases such as cystic fibrosis.
This experiment yielded unexpected results: modifying and stimulating the iBCs helped the ionocytes achieve higher levels of CFTR protein. This led the researchers to conclude that the ionocytes likely have been communicating and impacting other cells. Though what exactly they do is still a mystery awaiting to be solved, this discovery holds the key to curing the incurable cystic fibrosis, potentially so that its patients never will have to struggle from it—in possibly more than one way.