“The research is still in its early stages. But it’s very promising…”
A recent article in Arthritis and Rheumatology suggests that extracellular vesicles, which facilitate intercellular communication, could potentially contribute to fibrosis in systemic sclerosis.
Systemic sclerosis, also known as scleroderma, is characterized by fibrosis, a condition causing tissue to stiffen and harden. This can impact not only the skin but various other organs as well. Most investigations into this disease have explored the pathology and genesis of fibrosis. However, scientists from the Medical University of South Carolina are specifically focusing on identifying the factors that cause fibrosis to spread.
Their discoveries could potentially lead to the development of treatments to inhibit fibrosis spread and reduce the impact of scleroderma on patients.
Extracellular vesicles (EVs) are lipid-enclosed particles that transport nucleic acids, proteins, and other lipids between cells. Emerging studies indicate that these EVs could be manipulated for targeted drug delivery. As noted by the National Institutes of Health, EVs are effective carriers that can serve as promising drug delivery platforms, mainly because they do not trigger immune reactions as synthetic counterparts often do, and they are widely distributed in the body.
Carol Feghali-Bostwick, Ph.D., a prominent professor in MUSC’s rheumatology and immunology division and the lead author of the paper, lists three key features of scleroderma, an autoimmune connective tissue disorder. These include vascular abnormalities, immune system imbalance, and fibrosis. In fibrosis, cells overproduce extracellular matrix components such as collagen, leading to an excessive accumulation of these proteins, causing the tissues to harden. Consequently, organs such as the lungs become unable to expand sufficiently to collect the required oxygen.
Feghali-Bostwick further states that fibrosis from scleroderma is prototypical, resembling fibrosis caused by other diseases. Therefore, any advancements in treating fibrosis in scleroderma could also benefit patients with fibrosis stemming from other disorders.
For example, “Asthma is fibrosis of the airways, alcoholic liver cirrhosis is fibrosis of the liver,” Feghali-Bostwick explains. “Understanding scleroderma will open the door to better understanding all these other conditions as well. And new treatment developments are likely to be effective in those other conditions.”
Feghali-Bostwick and her colleagues examined the EVs originating from the lung tissues of scleroderma patients. They discovered that fibrotic lungs produce more EVs than healthy ones and that these EVs carry a higher amount of fibrotic proteins. This new study supports previous findings that correlate EVs and the fibrotic signals they carry.
The researchers also noted that EVs could stimulate inactive fibroblasts in healthy lungs, triggering fibrosis in these areas and initiating a cycle of fibrosis proliferation. Feghali-Bostwick emphasizes the need for further investigations to determine the impact of this process once it leaves the lungs.
While EVs serve as an efficient medium for cargo protection and intercellular communication, this very characteristic can also enhance the dangerous proliferation of fibrosis.
Feghali-Bostwick is optimistic about the clinical implications of these findings, as the interruption of EV communication or modification of their cargo could potentially be utilized as a therapeutic approach for patients suffering from scleroderma and fibrosis due to other conditions.
She adds, “The research is still in its early stages. But it’s very promising that we may be able to leverage EVs for treatment.”
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