New treatments for deadly lung disease could be revealed by 3D modeling

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New treatments for deadly lung disease could be revealed by 3D modeling

Press releases may be edited for formatting or style | September 15, 2020 3D Printing
A 3D bioengineered model of lung tissue built by University of Michigan researchers is poking holes in decades worth of flat, Petri dish observations into how the deadly disease pulmonary fibrosis progresses.

The causes of pulmonary fibrosis are not fully understood, but the condition is marked by scar tissue that forms inside the lungs. That scar tissue stiffens the walls of the lungs' air sacs, called alveoli, or, at advanced stages, can completely fill the alveolar spaces. Both scenarios make breathing difficult and decrease the amount of oxygen entering the bloodstream. Often the condition is irreversible, eventually causing lung failure and death.

Some clinicians are concerned that critically ill COVID-19 patients may develop a form of pulmonary fibrosis after a long stay in the ICU.

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Researchers are searching for better treatments. While they've managed to find some drugs that relieve symptoms or slow the progression in practice, they haven't been able to reliably replicate those results in today's 2D lab models. So they don't understand how or why those drugs are working, and they can't always predict which compounds will make a difference. The new research from U-M takes a step in that direction, and it starkly demonstrates how prior approaches have been ineffective.

The team showed that in some 2D models, drugs that are already known to be effective in treatment do not produce test results that show efficacy. Their 3D tissue engineered model of fibrotic lung tissue, however, shows that those drugs work.

Before their tests on drugs, they first performed studies to understand how tissue stiffness drives the appearance of myofibroblasts--cells that correlate with the progression of scarring.

"Even in cells from the same patient, we saw different outcomes," said Daniel Matera, a doctoral candidate and research team member. "When we introduced stiffness into the 2D testing environment, it activated myofibroblasts, essentially creating scar tissue. When we introduced that same kind of stiffness into our 3D testing environment, it prevented or slowed the activation of myofibroblasts, stopping or slowing the creation of scar tissue."

With the majority of pulmonary fibrosis research relying on 2D testing, he said, many have believed the high lung stiffness in patients is what should be targeted by treatments. U-M's research indicates that targeting stiffness alone may not hinder disease progression in patients, even if it works in a Petri dish.

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