Identification of Regenerative and Scar-Forming Cells May Lead to New Lung Therapies, Study Reports

Identification of Regenerative and Scar-Forming Cells May Lead to New Lung Therapies, Study Reports
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Lung disease cell types

Researchers have identified two types of lung cells, one with regenerative features and the other with scar-forming characteristics, according to a study published in the journal Cell.

The research team at the Perelman School of Medicine at the University of Pennsylvania obtained detailed knowledge about the function of the two cell types at the molecular level. That information could help scientists design a new generation of therapies for conditions such as idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD).

“We need better targets,” Edward E. Morrisey, a professor of Cell and Developmental Biology, said in a press release. “All we have now are blunt sledge hammers that don’t work,” he said of current treatments for lung conditions. The study’s senior author, Morrisey is also the director of the Penn Center for Pulmonary Biology.

In the search for new targets, researchers used RNA sequencing to analyze lung cells from mice. The method creates a profile of gene activity going on in a particular group of cells, or even isolated single cells. The study was titled “Distinct Mesenchymal Lineages and Niches Promote Epithelial Self-Renewal and Myofibrogenesis in the Lung.”

The idea behind the RNA sequencing approach was to gain insight into what the numerous cell types of the lung are doing.

“The lung is one of the most complex organs in the human body,” Morrisey said. This complexity makes diagnosing and treating lung conditions a challenging feat, he said.

The lungs have cells that specialize in delivering oxygen or eliminating carbon dioxide from blood. Some cells produce lubricants that cover airway surfaces. Others protect the lungs from intruding microbes or chemicals. And there are many more.

But the team did not analyze cells at random. They focused on mesenchymal cells, which scientists believe help support and maintain lung structure.

The sequencing analysis identified five varieties of these cells, and researchers homed in on two. By analyzing the cells’ molecular pathways and surface receptors, the team figured out what the cells were doing — and how.

One of them — called a mesenchymal alveolar niche cell, or MANC — turned out to be crucial to the regenerative properties of lung alveoli, which are the structures where gas exchange takes place.

The second cell, an Axin2+ myofibrogenic progenitor cell (AMP), gives rise to myofibroblasts when lungs are injured. Myofibroblasts create the scar tissue that is characteristic of IPF and certain other lung conditions.

“One of the most important functions of these cells is to balance the repair and regeneration response after injury, which occurs often due to the lung’s continual assault from the outside environment,” Morrisey said.

Researchers said MANCs could be found near alveoli, where they promoted the renewal of cells involved in gas exchange. Loss of these cells, or their inability to properly boost regenerative processes, might cause COPD, the team said. The AMPs, on the other hand, might contribute to IPF if their scar-forming activity gets out of control.

The team has now paired up with Edward Cantu, III, an associate professor of Surgery and the associate surgical director of Lung Transplantation at the university, to attempt to find these cell types in humans.

Further studies into the cells’ molecular characteristics might allow the team to move forward with targeted therapies focusing on MANCs to boost regeneration while blocking AMPs to reduce fibrosis.

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