Lung Stem Cells Offer Biomarkers for Earlier Lung Disease Diagnosis

Lung Stem Cells Offer Biomarkers for Earlier Lung Disease Diagnosis

The characterization of a type of pulmonary stem cells in adult lung tissue might lead to earlier diagnoses of chronic lung diseases, as researchers have identified factors in the cells that signal disease onset.

The behavior of the cells also provides researchers with insights into the processes leading to diseases such as lung fibrosis or pulmonary hypertension, which eventually may lead to the development of better treatments.

The cells were described in a study titled “Disruption of lineage specification in adult pulmonary mesenchymal progenitor cells promotes microvascular dysfunction,” published in the Journal of Clinical Investigation.

Although the cells, called pulmonary mesenchymal progenitor cells, have been the focus of many earlier research efforts, it has been difficult for researchers to pinpoint their specific role in disease processes.

This difficulty was caused by a lack of markers of how the cells develop into more mature cell types in healthy and diseased tissues. To overcome this, the research team used a so-called lineage mapping tool to track the markers of cell development under various conditions.

Researchers discovered that these cells are indeed an important contributor to disease processes.

“When these cells are abnormal, animals develop vasculopathy — a loss of structure in the microvessels and subsequently the lung. They lose the surfaces for gas exchange,” Susan Majka, PhD, associate professor of medicine at Vanderbilt University Medical Center in Tennessee and the study’s senior author, said in a press release.

Researchers have until now mainly seen changes in microscopic blood vessels that occur in lung disease as a process caused by changes in endothelial cells, which line the inside of the blood vessels, or smooth muscle cells surrounding the vessels. But the Vanderbilt research team figured that other cells must be involved.

The reason was that endothelial cells and muscles have reached the final stop on their developmental journey. They are what researchers call “terminally differentiated,” meaning that they are unlikely to turn into cells with other properties.

The stem cells that the team isolated — from both mice and human lungs — were sitting next to the microscopic blood vessels of the lung. There, they become active after a lung injury.

For instance, when the team exposed mice to a lung fibrosis-triggering compound, the cells started forming a blood vessel-like structure.

“It appears to be a form of ‘vascular mimicry,’ tubular structures that will circulate blood but are not normal blood vessels,” Majka said. “It’s a new form of angiogenesis that could get blood into the middle of fibrotic areas, but our studies ended early after the injury, during peak fibrosis, and we don’t know yet if it’s helping repair the injury or is actually detrimental.”

Maybe more importantly, the cellular studies allowed the team to discover biomarkers of lung disease — a finding with the potential to benefit patients relatively soon.

“With pulmonary vascular diseases, by the time a patient has symptoms, there’s already major damage to the microvasculature,” Majka said. These biomarkers could allow physicians to set a diagnosis earlier, which would allow for earlier treatment.

Since many lung diseases become progressively more severe, early treatment has the potential to slow worsening, or in some cases, even reverse disease processes.

But since the markers are also signs of processes that go awry, they might tell researchers more about how the diseases arise, thereby allowing them to develop new medications with the potential to stop disease development.

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