title: Primitive mesodermal cells with a neural crest stem cell phenotype predominate proliferating infantile haemangioma.
abstract: OBJECTIVE
  Infantile haemangioma is a tumour of the microvasculature characterised by aggressive angiogenesis during infancy and spontaneously gradual involution, often leaving a fibro-fatty residuum. The segmental distribution of a subgroup of infantile haemangioma, especially those associated with midline structural anomalies that constitute posterior fossa malformations-hemangiomas-arterial anomalies-cardiac defects-eye abnormalities-sternal cleft and supraumbilical raphe syndrome (PHACES), led us to investigate whether neural crest cells might be involved in the aetiology of this tumour.
  
  
  METHODS
  Immunohistochemical staining on paraffin embedded infantile haemangioma sections and immunocytochemical staining on cells derived from proliferating haemangioma cultures were performed.
  
  
  RESULTS
  The endothelium of proliferating infantile haemangioma contains abundant cells that express the neurotrophin receptor (p75), a cell surface marker that identifies neural crest cells, and also for brachyury, a transcription factor expressed in cells of the primitive mesoderm. The endothelium is also immunoreactive for the haematopoietic stem cell marker, CD133; the endothelial-haematopoietic stem/progenitor marker, CD34; the endothelial cell markers, CD31 and VEGFR-2; and the mesenchymal stem cell markers, CD29 and vimentin. Additionally, immunoreactivity for the transcription factors, Sox 9 and Sox 10, that are expressed by prospective neural crest cells was also observed. Cells from microvessel-like structures were isolated from in vitro cultured haemangioma tissue explants embedded in a fibrin matrix. Immunostaining of these cells showed that they retained expression of the same lineage-specific markers that are detected on the paraffin embedded tissue sections.
  
  
  CONCLUSIONS
  These data infer that infantile haemangioma is derived from primitive mesoderm and that the cells within the lesion have a neural crest stem cell phenotype, and they express proteins associated with haematopoietic, endothelial, neural crest and mesenchymal lineages. The authors propose a model to account for the natural progression of infantile haemangioma based upon the multipotent expression profile of the primitive mesoderm and their neural crest stem cell phenotype to form all the cell lineages detected during infantile haemangioma proliferation and involution.
authors.affiliation: School of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand.
authors.forename: Tinte
authors.initials: T
authors.lastname: Itinteang
authors.forename: Swee T
authors.initials: ST
authors.lastname: Tan
authors.forename: Helen
authors.initials: H
authors.lastname: Brasch
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Day
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000473:pathology; D006391:Hemangioma / Q000473:pathology*; D006801:Humans; D007223:Infant; D008648:Mesoderm / Q000473:pathology*; D039902:Multipotent Stem Cells / Q000473:pathology*; D009432:Neural Crest / Q000473:pathology*; D010641:Phenotype; D046509:Tissue Culture Techniques
chemical_list: D015415:Biomarkers