Researchers discover a mechanism to slow skin fibrosis in scleroderma

By Al Saint Jacques, MDLinx
Published November 1, 2016

Key Takeaways

New research has identified a possible mechanism behind the fibrosis that occurs in scleroderma, which might one day lead to effective treatment for the disease, according to a study recently published in the Journal of Clinical Investigation.

Scleroderma is an autoimmune disease characterized by fibrosis of the skin and one that can affect the blood vessels, lungs, and other organs. With limited treatment options available, those suffering from the disorder can face disabling hardening and tightening of their skin.

Experts at the Hospital for Special Surgery in New York City have reported that in laboratory research, a population of stem cells called 'adipose-derived stromal cells' (ADSCs) is reduced in number in the layer of fat sitting under the skin. It appears that loss of these ADSCs may contribute to the skin fibrosis characteristic of scleroderma.

In addition, the study authors discovered that the survival of those ADSCs that do remain beneath the skin in scleroderma are dependent on immune cells called 'dendritic cells'. Dendritic cells release a compound called lymphotoxin B that promotes ADSC survival. When antibodies that stimulate the lymphotoxin B receptor were administered with ADSCs to replenish the lost ADSCs, ADSC survival was found to be increased, suggesting a means for reversing the fibrosis of the skin.

"Injecting ADSCs is being tried in scleroderma; the possibility of stimulating the lymphotoxin B pathway to increase the survival of these stem cells is very exciting," explains lead study author Theresa T. Lu, MD, PhD. "By uncovering these mechanisms and targeting them with treatments, perhaps one day we can better treat the disease."

Dr. Lu also feels this strategy could be used to target stem-cells from other tissue sources in order to treat rheumatological and other conditions - such as lupus and rheumatoid arthritis - and also to facilitate bone and cartilage repair.

In the coming years, Dr. Lu and her colleagues hope to test the applicability of their work in human cells, which could provide scleroderma patients with a welcome treatment option if proven safe and effective. "Improving ADSC therapy would be a major benefit to the field of rheumatology and to patients suffering from scleroderma," she says.

Other authors from Hospital for Special Surgery include first author Jennifer Chia, Tong Zhu, Susan Chyou, Dragos Dasoveanu, and Camila Carballo, and HSS faculty members Drs. Jessica Gordon and Robert Spiera of the HSS Scleroderma and Vasculitis Center, and Dr. Scott Rodeo of the Sports Medicine and Shoulder Service.

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