Researchers engineer cells to help reverse pulmonary fibrosis

Gel-coated (red) mesenchymal stromal cells (yellow) can degrade collagen (green) over a distance in the presence of tumor necrosis factor-alpha.
Credit: Image: Jae-Won Shin and Sing-Wan Wong/UIC

Pulmonary fibrosis is a serious, mostly irreversible lung disease that can lead to scarring, or fibrosis, in the lungs due to damage or an unchecked immune response. But a new study shows that even after lung tissue has been damaged, it may be possible to reverse fibrosis and promote tissue repair.

Researchers engineered a thin microgel containing a small protein called tumor necrosis factor-alpha, or TNF-alpha, that could boost the therapeutic potential of mesenchymal stromal cells, or MSCs. Much like stem cells, MSCs have the capacity to self-renew and divide and develop into multiple specialized cell types. MSCs have also been studied for their potential to treat conditions like fibrosis. The microgel containing TNF-alpha acted as an inflammatory signal and encouraged MSCs to synthesize an enzyme called collagenase to degrade excess collagen and promote the restoration of the damaged, fibrotic lung tissue.

For optimization, the researchers designed a microfluidic device to encapsulate individual cells rapidly and consistently in the thin gel. In mouse models of fibrotic injury, researchers observed reduced indicators of scaring and increased indicators of healthy lung tissue, such as normal collagen levels and architecture, among mice treated with encapsulated individual MSCs in thin gel with TNF-alpha. The study, published in Nature Biomedical Engineering, was partly funded by NHLBI.