Discovery May Bolster an Experimental Stem Cell Therapy for Scleroderma

Stimulating skin fat stem cells eased skin fibrosis in a scleroderma mouse model, suggesting the treatment may be an option for patients. Injections of such cells are already being tested in scleroderma, and the new finding could be a way of improving cell survival after injection.

The study, “Dendritic cells maintain dermal adipose–derived stromal cells in skin fibrosis,” was published in the Journal of Clinical Investigation.

In scleroderma, skin fibrosis is accompanied by destruction of the fat tissue. This tissue usually contains a type of stem cell, called adipose-derived stromal cell, or ADSC. So far, studies have not explored whether ADSCs disappear as the fat tissue is destroyed.

Using a mouse model of scleroderma, researchers at the Hospital for Special Surgery in New York City showed that they are, indeed, lost. The mice had lower numbers of ADSC cells in their skin, and the cells that remained were dependent on signals from another cell type to survive.

This other cell produces a factor called lymphotoxin B, which was the signal that aided ADSC survival. This was good news, the research team figured, as lymphotoxin B signaling could be used to reverse the cell loss.

To test the idea, researchers injected scleroderma mice with ADSCs, along with antibodies that stimulated the lymphotoxin B receptor. This not only increased the number of ADSCs that survived the transplant, but also reduced skin fibrosis.

“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,” Theresa Lu, MD, PhD, senior author of the study, said in a news release.

“By uncovering these mechanisms and targeting them with treatments, perhaps one day we can better treat the disease,” she added.

The research team next plans to test their discoveries in human cells. “Improving ADSC therapy would be a major benefit to the field of rheumatology and to patients suffering from scleroderma,” Lu said.

Lu also believes that the same approach could also be used to stimulate other types of stem cells, important in other rheumatological or autoimmune conditions.