title: Blocking of stromal cell-derived factor-1 reduces neoangiogenesis in human endometriosis lesions in a mouse model.
abstract: OBJECTIVE
  Endometriosis affects 5-10% of women and is characterized by the growth of endometrial tissue outside of the uterus. Establishing new blood supply is a fundamental requirement for endometriosis lesion growth. Endothelial progenitor cells (EPCs), recruited by stromal cell-derived factor-1 (SDF-1), contribute to neoangiogenesis in endometriotic lesions. We hypothesized that SDF-1 is central to the neoangiogenesis and survival of endometriotic lesions, and blocking of SDF-1 will reduce vascularization of lesions in a mouse model.
  
  
  METHODS
  Using immunohistochemistry, we evaluated SDF-1 and CD34(+) EPCs in human endometriotic lesions and normal endometrium samples. EPCs were co-localized using CD34 and VEGFR2. Effects of SDF-1 blocking on endometriotic lesion survival were assessed in BALB/c-Rag2(-/-) /IL2rγ(-/-) mice engrafted with human endometrium and treated with SDF-1-blocking antibody or an isotype control. Weekly blood samples from experimental mice were analyzed for cytokines and EPCs.
  
  
  RESULTS
  SDF-1 and CD34(+) EPCs were abundant in human endometriotic lesions compared with eutopic endometrium. In our mouse model, SDF-1-blocking antibody reduced CD31(+) microvessels compared with isotype control.
  
  
  CONCLUSIONS
  Blocking SDF-1 reduces neovascularization and survival of lesions in a mouse model of endometriosis.
authors: Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.
authors: Sophia
authors: S
authors: Virani
authors: Andrew K
authors: AK
authors: Edwards
authors: Richard
authors: R
authors: Thomas
authors: Timothy
authors: T
authors: Childs
authors: Chandrakant
authors: C
authors: Tayade
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D018952:Antigens, CD34 / Q000378:metabolism; D054377:Chemokine CXCL12 / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D004715:Endometriosis / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D004717:Endometrium / Q000473:pathology / Q000637:transplantation; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D005260:Female; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D055806:Microvessels / Q000187:drug effects* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D014183:Transplantation, Heterologous; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D019138:Antibodies, Blocking; D018952:Antigens, CD34; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; C507942:Il2rg protein, mouse; D053631:Interleukin Receptor Common gamma Subunit; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Angiogenesis; endometriosis; endothelial progenitor cell; stromal cell-derived factor-1