Microgel coating gives a boost to donor cells in reversing lung fibrosis

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Ice-covered (red) mesenchymal stromal cells can degrade collagen (green) at a distance with the presence of tumor-alpha necrosis factor. Credits: Jae-Won Shin and Sing-Wan Wong / UIC

Researchers at the University of Illinois at Chicago have shown that, even after damaging lung tissue, it may be possible to reverse fibrosis and promote tissue repair by treatment with microgel-coated mesenchymal stromal cells.

Pulmonary fibrosis is a chronic disease caused by environmental toxins, medications, or medical conditions such as pneumonia and rheumatoid arthritis. It is characterized by scar formation due to damage or an uncontrolled immune response, and can cause mild to severe breathing difficulties and oxygen deprivation. Fibrosis is currently believed to be mostly irreversible, as current pharmacological treatments are only slightly effective in controlling symptoms and generally cause significant side effects.

Mesenchymal stromal cells, or MSCs, are multipotent and renew themselves and their potential to treat conditions such as fibrosis have been studied.

“Although previous studies tested the therapeutic effects of MSCs, which are known to suppress inflammation and adapt to different tissue environments, their effectiveness has so far been limited to the early stages of the disease, when levels of inflammation are high and scar tissue is still forming, “said Jae-Won Shin, assistant professor of pharmacology and bioengineering at the UIC at the College of Medicine and corresponding author of the study. “Our focus was to optimize MSC-based therapy to work after reducing inflammation, which is when fibrosis is diagnosed in most people.”

As described in a new article published in Biomedical Engineering of Nature, UIC researchers designed a thin microgel that, when specifically designed, can increase the therapeutic potential of MSCs to degrade and regenerate healthy tissues in mouse fibrosis models.

Shin and colleagues designed the microgel, which is as soft as healthy lung tissue, and incorporated a small protein called tumor necrosis factor-alpha. Also known as TNF-alpha, this protein acts as an inflammatory signal that encourages MSCs to synthesize collagenase. Collagenase is an enzyme that degrades excess collagen in fibrotic tissues and promotes the restoration of damaged tissues.

To optimize MSCs with microgel, UIC researchers designed a microfluidic device to encapsulate quickly and steadily on thin ice.

“We miniaturized on a small scale, the individual cell, which is important for the delivery of therapeutic treatment to the small airways of the lungs,” said Sing-Wan Wong, lead author of the study, an associate postdoctoral researcher at the UIC in the department of pharmacology and regenerative medicine.

In models of fibrotic lesions, UIC researchers observed a reduction in scar indicators and an increase in health indicators , such as normal collagen levels and architecture, only among MSC-treated mice coated with their gel incorporated into TNF-alpha by single-cell encapsulation.

“This is really one of the first scientific demonstrations that collagen levels can be normalized well after a fibrotic injury and that the cellular environment, not just the “Our results suggest a feasible approach to predictively program cellular functions to achieve the desired therapeutic outcomes,” Shin said.


According to the study, targeting the mechanosensitive protein could treat pulmonary fibrosis


More information:
Sing Wan Wong et al, Inhibition of aberrant tissue remodeling by mesenchymal stromal cells individually coated with soft gels showing defined chemomechanical indications, Biomedical Engineering of Nature (2021). DOI: 10.1038 / s41551-021-00740-x

Citation: Microgel coating gives a boost to donor cells in the reversal of pulmonary fibrosis (2021, June 8) recovered on June 8, 2021 at https://medicalxpress.com/news/2021-06- microgel-coating-donor-cells-boost.html

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