Chronic Obstructive Pulmonary Disease (COPD) is a progressive disease of the lungs characterized by inflammation, fibrosis, excessive mucus production, and destruction of the alveoli where gas exchange occurs. COPD is a leading cause of death, with figures suggesting there were 251 million people worldwide living with the disease in 2016. That makes the disease the biggest killer worldwide. While the factors that contribute to the development of the disease are known, the root cause is poorly understood.
While there are medications that can be provided to control inflammation and improve breathing, treatment is concerned with managing the symptoms and slowing the progression of the disease, which will ultimately prove fatal. There is currently no cure and no treatment that can stop the progression of the disease.
Two leading stem cell experts have been investigating the cause of COPD and have shown that patients with COPD have high numbers of abnormal stem cells in the lungs, which could serve as a potential target for new treatments.
The study was conducted by Frank McKeon, professor of biology and biochemistry and director of the Stem Cell Center, and Wa Xian, research associate professor at the Stem Cell Center. Using stem cells taken from fluid collected from the lungs of patients diagnosed with COPD, they identified three variant cells that were present in all COPD patients that drive the key features of the disease.
One of these cell types produces large amounts of mucins, which cause blockages in the small airways. The other two cell types are responsible for driving fibrosis and inflammation, both of which result in degradation of lung function. The researchers found that COPD patients do have normal stem cells in the lugs, but the majority of stem cells are made up of the three variant cells.
The metaplastic lesions found in the lungs of COPD patients were shown to be driven by the abnormal stem cells. These lesions are thought by many scientists to be a secondary effect of COPD, without a causal link to the pathology of the disease.
The two researchers have developed techniques for cloning lung stem cells and have been doing so for a decade. Postdoctoral fellow and team member, Wei Reo, found that when these cloned abnormal stem cells were transferred into the lungs of immunodeficient subjects, they triggered distinct metaplastic lesions of the types seen in COPD patients and also triggered the three pathologies of COPD, excessive mucus secretion, chronic inflammation, and fibrosis of lung tissue.
Rather than the metaplastic lesions being secondary consequences of the disease, the researchers found they were actually driving the disease. Now that the root cause of COPD has been discovered, the researchers have started screening a range of drug-like molecules that could be used to target the abnormal stem cells, which could halt the progression of the disease. It may also be possible, by eliminating the abnormal stem cells, to see lung function improve in COPD patients through the regeneration of lung tissue by normal, healthy stem cells.
One study conducted in 2011 on H1N1 influenza victims, showed the lungs are capable of regeneration. “It’s quite remarkable. In the deep lung, the distal airway stem cells gave rise to both the distal tubes and the alveoli and our research indicates those are the stem cells that make it possible for lungs to regenerate on their own,” explained McKeon.
“As we now know the specific cells responsible for COPD pathology, we can target them, much as we would cancer, with specific drugs that selectively kill them off and leave the normal cells to regenerate normal lung tissue,” said Xian.
You can read more about the study in the paper – Regenerative Metaplastic Clones in COPD Lung Drive Inflammation and Fibrosis – which was recently published in the journal Cell. DOI: 10.1016/j.cell.2020.03.047