Single-cell cloning can lead to new therapies for COPD

Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of death around the world. Now, two stem cell experts have discovered a large number of abnormal stem cells found in the lungs of COPD patients.

Single-cell cloning can lead to new therapies for COPD
Although Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of death worldwide, little has been written or understood about the root cause of it until now. Image Credit: University of Houston.

Frank McKeon, Director of the Stem Cell Center and Professor of Biology and Biochemistry, and Wa Xian, a Research Associate Professor at the Stem Cell Center, made this discovery by using single-cell cloning of lung stem cells.

The duo is currently targeting these stem cells to develop new therapeutics.

We actually found that three variant cells in all COPD patients drive all the key features of the disease. One produces tremendous amounts of mucins which block the small airways, while the other two drive fibrosis and inflammation which together degrade the function of the lung. These patients have normal stem cells, though not many of them, but they are dominated by the three variant cells that together make up the disease.”

Wa Xian, Research Associate Professor, Stem Cell Center, University of Houston

Xian has reported the study in the forthcoming May 14 issue of the Cell journal.

COPD is a progressive inflammatory disorder of the lungs characterized by chronic bronchitis, fibrosis, inflammation, small airway occlusion, and destruction of alveoli—tiny air sacs present in the lungs and exchange molecules of carbon dioxide and oxygen in the blood.

In fact, the Global Burden of Disease Study had reported as many as 251 million cases of COPD in 2016 worldwide.

It’s a frustrating disease to care for. We can try and improve the symptoms, but we don’t have anything that can cure the disease or prevent death,

Mark Metersky, Health pulmonologist, University of Connecticut (UConn)

Although COPD accounts for a higher mortality rate when compared to any other singular disease on Earth, not much had been understood or written about the root cause of this disease.

Since the past 10 years, Xian and McKeon have been developing a technology for cloning the stem cells of both the lungs and airways, and they had observed that various parts of the airways provide related but distinguishable different stem cells.

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.”

Frank McKeon, Professor, Depart of Biology and Biochemistry, University of Houston

In 2011, Xian and McKeon had discovered lung regeneration during their studies of subjects who were recovering from H1N1 influenza viral infections. The H1N1 virus was almost identical to that which triggered the 1918 pandemic.

In contrast to normal lungs, the duo discovered that COPD lungs were flooded with three unique variant lung stem cells that are inclined to form metaplastic lesions known for inhabiting COPD lungs, but considered by many researchers as a secondary effect without a causal connection to COPD pathology.

When Wei Rao—the team’s postdoctoral fellow—implanted each one of the COPD clones into immunodeficient patients, the researchers found that these clones not only resulted in the distinct metaplastic lesions of COPD but also individually stimulated the triad of COPD pathologies such as fibrosis, mucus hypersecretion, and chronic inflammation.

McKeon added that “The long-overlooked metaplastic lesions in COPD were, in fact, driving the disease rather than merely secondary consequences of the condition.

Now, since the researchers are aware of the identity of the cells that cause the obstruction of small airways, fibrosis, and inflammation, they are working hard to screen them against libraries of drug-like molecules to find out novel therapeutics.

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.”

Wa Xian, Research Associate Professor, Stem Cell Center, University of Houston

Source:
Journal reference:

Rao, W., et al. (2020) Regenerative Metaplastic Clones in COPD Lung Drive Inflammation and Fibrosis. Cell. doi.org/10.1016/j.cell.2020.03.047.

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