Stem Cell Transplantation Eases Skin Inflammation in Systemic Sclerosis

Autologous hematopoietic stem cell transplantation, an intensive immune-resetting therapy already known to reduce cutaneous fibrosis in systemic sclerosis, also appears to act on the epidermis, the outermost layer of the skin, according to a new study published in Advances in Rheumatology. The research, led by Djúlio C. Zanin-Silva and colleagues with senior authorship from Kelen C. R. Malmegrim and Maria Carolina Oliveira, examined whether the procedure modulates epidermal inflammation and keratinocyte activity, an aspect the authors describe as remaining underexplored despite documented effects on dermal architecture.

The study retrospectively evaluated 29 patients with severe systemic sclerosis who underwent autologous hematopoietic stem cell transplantation. Clinical data, skin biopsies, and serum samples were collected before transplantation and again at six months afterward, and a healthy control group was included for comparison. Skin biopsies were examined qualitatively for epidermal thickness and for expression of inflammatory and proliferation markers, including S100A9, TNF-α, IL-1α, and Ki-67, using immunohistochemistry. Serum molecules associated with inflammation and epidermal disturbances were quantified with Multiplex and ELISA assays.

The clinical outcome was clear: the researchers reported significant improvement in the modified Rodnan Skin Score, a standard measure of skin thickening, after transplantation. Epidermal thickness also decreased following the procedure, although the authors note that it did not return to the values observed in healthy controls. This partial normalization is consistent with the therapy producing meaningful but incomplete restoration of skin structure at the six-month time point.

At baseline, before treatment, serum levels of several immune and epithelial signaling molecules were higher in the patients than in healthy controls: EGF, IL-1α, CCL-3, TNF-α, IFN-γ, IL-6, and IL-17 were all elevated. After transplantation, however, the picture diverged across this panel. Serum levels of TNF-α, IFN-γ, IL-6, and IL-17 did not change following the procedure, suggesting that these circulating inflammatory signals persisted despite the clinical improvement in the skin.

Other markers moved in the direction of healthy values. EGF and IL-1α, both implicated in epithelial activation, decreased significantly after transplantation but remained higher than in the control group. Only two molecules, the chemokine CCL-3 and connective tissue growth factor, or CTGF, decreased and normalized fully after the procedure. Meanwhile, serum concentrations of CCL-5, CCL-2, IL-8, and HGF were not different from healthy controls at either time point and did not alter after transplantation.

The study also uncovered a statistical link between the skin score and one immune marker: the change in modified Rodnan Skin Score and the change in serum IL-1α concentrations were positively correlated after transplantation. In other words, patients whose skin scores improved more tended to show larger drops in this epithelial activation marker, although the authors present this as an association rather than evidence of a causal relationship.

To probe functional effects on keratinocytes, the team turned to laboratory experiments. Serum samples from the patients and from healthy controls were used to stimulate human HaCaT keratinocyte cell cultures, and the pro-inflammatory cytokine CCL-5 was then quantified in the culture supernatants. When the keratinocytes were exposed to serum from patients at baseline, the CCL-5 levels were not different from those seen with control serum. However, when the cells were exposed to serum collected after transplantation, there was a significant reduction in CCL-5 concentrations.

That result is notable because it suggests that something in the post-transplant serum environment changed in a way that alters how keratinocytes respond, even though baseline serum from patients did not provoke more CCL-5 release than control serum in the first place. The authors interpret this as a decrease in CCL-5 release by stimulated keratinocytes following the therapy, one of the three main strands of their findings alongside the reduced epidermal thickness and the lowered serum markers of epithelial activation.

Taken together, the authors conclude that autologous hematopoietic stem cell transplantation reduces epidermal thickness and inflammation in the skin of systemic sclerosis patients, lowers serum markers of epithelial activation, and decreases CCL-5 release by stimulated keratinocytes. They suggest that, beyond resetting the immune system, the procedure modulates epithelial disturbances associated with inflammation and fibrosis, supporting its therapeutic potential in this disease. The findings come from a retrospective analysis of a single patient group with a six-month follow-up and qualitative biopsy assessment, and the article is being shared early as a peer-reviewed, accepted version of record, so the results should be read with that scope in mind.

Subject of Research: Effects of autologous hematopoietic stem cell transplantation on epidermal inflammation and fibrosis mechanisms in systemic sclerosis

Article Title: Autologous hematopoietic stem cell transplantation modulates epidermal-related inflammation/fibrosis mechanisms in systemic sclerosis patients

Article References: Zanin‑Silva, D. C., Sabbadini, S. G., Públio, G. A., dos Santos, N. C. D., Forti, P. D., Lima, F. R., de Paula, N. A., Santana‑Gonçalves, M., De Santis, P. B., Dias, J. B. E., Moraes, D. A., Ramalho, L., Malmegrim, K. C. R., & Oliveira, M. C. (2026). Autologous hematopoietic stem cell transplantation modulates epidermal-related inflammation/fibrosis mechanisms in systemic sclerosis patients. Advances in Rheumatology. https://doi.org/10.1186/s42358-026-00579-3

Image Credits: AI Generated

DOI: 10.1186/s42358-026-00579-3

Keywords: systemic sclerosis, autologous hematopoietic stem cell transplantation, epidermal thickness, fibrosis, keratinocytes, CCL-5, IL-1alpha, EGF, modified Rodnan Skin Score, immunohistochemistry, HaCaT keratinocytes, skin biopsies