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Generation and Grafting of Tissue-engineered Vessels in a Mouse Model
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Defective vasculogenesis in systemic sclerosis.

Masataka Kuwana1, Yuka Okazaki, Hidekata Yasuoka

  • 1Institute for Advanced Medical Research Keio University School of Medicine, Tokyo, Japan. kuwanam@sc.itc.keio.ac.jp

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Systemic sclerosis patients have fewer circulating endothelial precursors, impairing blood vessel repair. This suggests defective vasculogenesis contributes to their vascular disease and offers potential therapeutic targets.

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Area of Science:

  • Cardiovascular Biology
  • Immunology
  • Regenerative Medicine

Background:

  • Systemic sclerosis (SSc) is characterized by vascular damage, including reduced capillary density and vessel obliteration.
  • Vasculogenesis, the formation and repair of blood vessels, relies on circulating endothelial precursors (CEP).
  • Impaired vasculogenesis may underlie the vascular pathology observed in SSc.

Purpose of the Study:

  • To investigate whether vasculogenesis is impaired in patients with systemic sclerosis.
  • To quantify circulating endothelial precursors (CEP) in SSc patients compared to controls.
  • To assess the differentiation potential of CEP in SSc.

Main Methods:

  • Quantified CEP (CD34+, CD133+, VEGFR2+) in peripheral blood of SSc, rheumatoid arthritis, and healthy control groups using flow cytometry.
  • Measured circulating angiogenic factors via ELISA.
  • Assessed CEP differentiation capacity by in-vitro maturation and von Willebrand factor expression.

Main Results:

  • SSc patients exhibited significantly lower absolute numbers of CEP compared to rheumatoid arthritis patients and healthy controls (p<0.0001).
  • Paradoxically, circulating angiogenic factor concentrations were elevated in SSc patients.
  • The proportion of CEP capable of differentiating into endothelial cells was significantly reduced in SSc patients (p<0.0001).

Conclusions:

  • Defective vasculogenesis, indicated by a reduced number and impaired differentiation of CEP, likely contributes to the vasculopathy seen in systemic sclerosis.
  • Dysregulated vasculogenesis may be implicated in other vascular disorders, including cancer and atherosclerosis.
  • CEP represent a potential therapeutic target for managing ischemic complications in SSc.