How Stem Cell Therapy Works to Ease Skin Fibrosis in SSc Detailed

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Autologous hematopoietic stem cell transplant (AHSCT) eases skin scarring in people with diffuse systemic sclerosis (SSc) by tweaking the levels of molecules involved in tissue remodeling and inflammation, a study from Brazil reported.

The study, “Autologous hematopoietic stem cell transplantation promotes connective tissue remodeling in systemic sclerosis patients,” was published in the journal Arthritis Research and Therapy.

Stem cell transplants are being studied as a possible way to treat scleroderma patients, including those with severe progressive disease. It is thought that stem cells may be able to change or reset the body’s immune system.

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In scleroderma, the immune system is autoreactive, turning against the body’s own connective tissue that gives structure and support to organs. As a result, the tissues harden and undergo fibrosis or scarring.

Studies have shown that transplants of hematopoietic stem cells, a type of stem cell usually found in the bone marrow that can develop into any type of blood cell, can ease skin fibrosis. The procedure involves harvesting a patient’s stem cells from their bone marrow, an autologous procedure, and infusing them back into the bloodstream after suppressing the existing immune cells using a chemotherapy such as cyclophosphamide (brand names, Cytoxan and Neosar).

“However, basic mechanisms associated with the therapeutic efficacy of the procedure are not entirely understood,” the researchers wrote.

The scientists looked at data covering 39 SSc patients, 32 women and seven men, who underwent AHSCT at the University of São Paulo from 2011 to 2016.

All had diffuse scleroderma, a form of SSc usually marked by extensive skin fibrosis on the arms, legs, and trunk, and a higher risk of organ damage. It is generally more severe and worsens more quickly than limited scleroderma.

Patients’ median age at the time of AHSCT was 35, and their median disease duration was two years.

Data on skin fibrosis, assessed using the modified Rodnan skin score (mRSS), were available before and one year after AHSCT. When the researchers compared the data, they found that skin fibrosis had eased from a mean 24 points to 16 points within one year.

Looking more closely at forearm skin samples, they found a “significant decrease in skin thickness … and collagen density.” Collagen, a protein, plays a key role in fibrosis.

The change in the amount of collagen correlated positively with the mRSS, meaning the lower the amount of collagen, the greater the reduction in skin fibrosis.

“AHSCT effectively improves clinically assessed skin thickening and collagen turnover, and connective tissue remodeling,” the researchers wrote.

Levels of proteins in the family of matrix metalloproteinases, which can cut the matrix where cells attach and help in wound healing, were increased in the skin after AHSCT. In turn, blood levels of PDGF-AA and PDGF-BB — two proteins that promote cell growth in fibrotic tissue — were lower.

Blood levels of S100A9, a protein released by skin cells under inflammatory stress, were also higher in SSc patients before treatment than in healthy individuals. After AHCST, the levels of S100A9 in patients normalized.

“The therapeutic effects of AHSCT on skin fibrosis are related to changes in molecules associated with connective tissue maintenance and inflammation in SSc,” the researchers concluded.

“In addition to the primary mechanism for controlling immunological autoreactivity, AHSCT enables other therapeutic pathways that together contribute to the favorable clinical outcomes of SSc patients,” they added.