Researchers at the University of Illinois at Chicago have shown that even after lung tissue has been damaged, it may be possible to reverse fibrosis and promote tissue repair through treatment with mesenchymal stromal cells. coated with microgel.
Pulmonary fibrosis is a chronic disease caused by environmental toxins, drugs, or medical conditions like pneumonia and rheumatoid arthritis. It is characterized by the formation of scar tissue due to damage or an uncontrolled immune response, and it can cause mild to severe breathing difficulties and oxygen deprivation. Fibrosis is currently believed to be primarily irreversible, as current drug treatments are only moderately effective in managing symptoms and usually cause significant side effects.
Mesenchymal stromal cells, or MSCs, are multipotent and self-renewing, just like stem cells, and have been studied for their potential to treat conditions like fibrosis.
“While previous studies have 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 inflammation are high and scar tissue is still forming, ”said Jae-Won Shin, assistant professor of pharmacology and bioengineering at UIC College of Medicine and corresponding author of the study. The approach was to optimize MSC-based therapies to work after inflammation has reduced, that is, when most people are diagnosed with fibrosis. “
As described in a new paper published in Nature Biomedical Engineering, UIC researchers have designed a thin microgel that, when specifically designed, can increase the therapeutic potential of MSCs to degrade scar tissue and regenerate tissue. healthy in murine models of fibrosis.
Shin and his 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 breaks down excess collagen in fibrous tissue and helps restore damaged tissue.
To optimize MSCs with the microgel, UIC researchers designed a microfluidic device to encapsulate individual cells quickly and consistently in the thin gel.
“We have miniaturized the individual cell on a small scale, which is important for delivering therapy to the tiny airways of the lungs,” said study lead author Sing-Wan Wong, research associate. postdoctoral fellow at UIC in the Department of Pharmacology and Regenerative Medicine.
In fibrotic lesion models, UIC researchers observed reduced indicators of wound healing and increased indicators of healthy lung tissue, such as normal collagen levels and architecture, only in mice treated with MSC coated with their gel incorporated into TNF-alpha via a unique cellular encapsulation. .
“This is truly one of the first scientific demonstrations that collagen levels can be well normalized after fibrotic injury, and that the cellular environment, not just the cells themselves, can be designed at the unicellular level of a. precise way, ”Shin said. . “Our results suggest a feasible approach to predictively program cellular functions for desired therapeutic outcomes.”
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