To find effective treatments, researchers first screen libraries of pharmaceutical compounds. Today, they typically do that on cells cultured on flat plastic or hydrogel surfaces, but these settings often do a poor job of recreating what happens in the human body.
Brendon Baker, assistant professor in the U-M Department of Biomedical Engineering, and his team took a tissue engineering approach. They reconstructed 3D lung interstitium, or connective tissue, the home of fibroblasts and location where fibrosis begins. Their goal was to understand how mechanical cues from lung tissue affect fibroblast behavior and disease progression.
"Recreating the 3D fibrous structure of the lung interstitium allowed us to confirm effective drugs that wouldn't be identified as hits in traditional screening settings," Baker said.
At the center of the pulmonary fibrosis mystery is the fibroblast, a cell found in the lung interstitium that is crucial to healing but, paradoxically, can also drive disease progression. When activated, after an injury or when disease is present, they become myofibroblasts. Regulated properly, they play an important role in wound healing, but when misregulated, they can drive chronic disease. In the case of pulmonary fibrosis, they cause the stiffening of lung tissue that hampers breathing.
"Our lung tissue model looks and behaves similarly to what we have observed when imaging real lung tissue," Baker said. "Patient cells within our model can actively stiffen, degrade or remodel their own environment just like they do in disease."
Back to HCB News
