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Dermal cellular senescence and EndMT in patients with systemic sclerosis undergoing cyclophosphamide or aHSCT

Yu-Hsiang Chiu1,2, Marijke van Dijk3, Roel Goldschmeding3

  • 1Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.

Rheumatology (Oxford, England)
|December 10, 2024
PubMed
Abstract

Insights

Autologous haematopoietic stem cell transplantation (aHSCT) and cyclophosphamide (CYC) reduced skin thickening and endothelial-to-mesenchymal transition (EndMT) in systemic sclerosis (SSc). aHSCT showed a more pronounced effect on EndMT and fibrosis compared to CYC.

Area of Science:

  • Rheumatology
  • Dermatology
  • Cell Biology

Background:

  • Cellular senescence and endothelial-to-mesenchymal transition (EndMT) are key profibrotic processes in systemic sclerosis (SSc).
  • The impact of treatments on these cellular pathways in SSc remains largely uncharacterized.

Purpose of the Study:

  • To investigate the effects of autologous haematopoietic stem cell transplantation (aHSCT) and pulse cyclophosphamide (iv CYC) on cellular senescence and EndMT in diffuse cutaneous SSc (dcSSc).
  • To correlate treatment response with specific cellular markers and histopathological findings.

Main Methods:

  • Skin biopsies from dcSSc patients treated with aHSCT or iv CYC were analyzed before and 6 months after treatment.
  • Histopathological examination assessed fibrosis, inflammation, senescence, EndMT, and tissue remodelling, including markers like uPAR, P21, and CTGF.

Main Results:

  • Both aHSCT and iv CYC treatments led to a significant reduction in skin thickening (modified Rodnan skin score) and EndMT.
  • aHSCT demonstrated a more pronounced decrease in EndMT and fibrosis markers compared to iv CYC.
  • Poor treatment response was associated with specific baseline levels of CTGF and P21, and changes in these markers post-treatment.

Conclusions:

  • aHSCT and iv CYC effectively reduce skin fibrosis and attenuate EndMT in dcSSc patients.
  • While both treatments impact EndMT, cellular senescence was not significantly altered differently between the groups.
  • EndMT, uPAR, CTGF, and vascularity are key indicators of fibrotic activity and treatment response in SSc.
Keywords:
autologous haematopoietic stem cell transplantationfibrosispathologysclerodermasenescencesystemic sclerosis

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