title: Capillary regeneration in scleroderma: stem cell therapy reverses phenotype?
abstract: BACKGROUND
  Scleroderma is an autoimmune disease with a characteristic vascular pathology. The vasculopathy associated with scleroderma is one of the major contributors to the clinical manifestations of the disease.
  
  
  RESULTS
  We used immunohistochemical and mRNA in situ hybridization techniques to characterize this vasculopathy and showed with morphometry that scleroderma has true capillary rarefaction. We compared skin biopsies from 23 scleroderma patients and 24 normal controls and 7 scleroderma patients who had undergone high dose immunosuppressive therapy followed by autologous hematopoietic cell transplant. Along with the loss of capillaries there was a dramatic change in endothelial phenotype in the residual vessels. The molecules defining this phenotype are: vascular endothelial cadherin, a supposedly universal endothelial marker required for tube formation (lost in the scleroderma tissue), antiangiogenic interferon alpha (overexpressed in the scleroderma dermis) and RGS5, a signaling molecule whose expression coincides with the end of branching morphogenesis during development and tumor angiogenesis (also overexpressed in scleroderma skin. Following high dose immunosuppressive therapy, patients experienced clinical improvement and 5 of the 7 patients with scleroderma had increased capillary counts. It was also observed in the same 5 patients, that the interferon alpha and vascular endothelial cadherin had returned to normal as other clinical signs in the skin regressed, and in all 7 patients, RGS5 had returned to normal.
  
  
  CONCLUSIONS
  These data provide the first objective evidence for loss of vessels in scleroderma and show that this phenomenon is reversible. Coordinate changes in expression of three molecules already implicated in angiogenesis or anti-angiogenesis suggest that control of expression of these three molecules may be the underlying mechanism for at least the vascular component of this disease. Since rarefaction has been little studied, these data may have implications for other diseases characterized by loss of capillaries including hypertension, congestive heart failure and scar formation.
authors.affiliation: Department of Pathology, University of Washington, Seattle, Washington, United States of America. flemij@u.washington.edu
authors.forename: Jo N
authors.initials: JN
authors.lastname: Fleming
authors.forename: Richard A
authors.initials: RA
authors.lastname: Nash
authors.forename: D O
authors.initials: DO
authors.lastname: McLeod
authors.forename: David F
authors.initials: DF
authors.lastname: Fiorentino
authors.forename: Howard M
authors.initials: HM
authors.lastname: Shulman
authors.forename: M Kari
authors.initials: MK
authors.lastname: Connolly
authors.forename: Jerry A
authors.initials: JA
authors.lastname: Molitor
authors.forename: Gretchen
authors.initials: G
authors.lastname: Henstorf
authors.forename: Robert
authors.initials: R
authors.lastname: Lafyatis
authors.forename: David K
authors.initials: DK
authors.lastname: Pritchard
authors.forename: Lawrence D
authors.initials: LD
authors.lastname: Adams
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Furst
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Schwartz
mesh_terms: D002196:Capillaries / Q000502:physiology*; D006801:Humans; D010641:Phenotype; D012038:Regeneration; D045743:Scleroderma, Diffuse / Q000601:surgery*; D033581:Stem Cell Transplantation