Increased circulating AC133+ CD34+ endothelial progenitor cells in children with hemangioma.
Hemangioma is the most common soft-tissue tumor of infancy. Despite the frequency of these vascular tumors, the origin of hemangioma-endothelial cells is unknown. Circulating endothelial progenitor cells (EPCs) have recently been identified as vascular stem cells with the capacity to contribute to postnatal vascular development. We have attempted to determine whether circulating EPCs are increased in hemangioma patients and thereby provide insight into the role of EPCs in hemangioma growth.


RESULTS
Peripheral blood mononuclear cells (PBMCs) were isolated from hemangioma patients undergoing surgical resection (N = 5) and from age-matched controls (N = 5) undergoing strabismus correction surgery. PBMCs were stained with fluorescent-labeled antibodies for AC133, CD34, and VEGFR2/KDR. Fluorescent-labeled isotype antibodies served as negative controls. Histologic sections of surgical specimens were stained with the specific hemangioma markers Glut1, CD32, and merosin, to confirm the diagnosis of common hemangioma of infancy. EPCs harvested from healthy adult volunteers were stained with Glut1, CD32, and merosin, to assess whether cultured EPCs express known hemangioma markers. Hemangioma patients had a 15-fold increase in the number of circulating CD34 AC133 dual-staining cells relative to controls (0.78+/-0.14% vs.0.052+/-0.017%, respectively). Similarly, the number of PBMCs that stained positively for both CD34 and KDR was also increased in hemangioma patients (0.49+/-0.074% vs. 0.19+/-0.041% in controls). Cultured EPCs stained positively for the known hemangioma markers Glut1, CD32, merosin.


CONCLUSIONS
This is the first study to suggest a role for EPCs in the pathogenesis of hemangioma. Our results imply that increased levels of circulating EPCs may contribute to the formation of this vascular tumor.
Kleinman
Mark E
ME
Laboratory of Microvascular Research and Vascular Tissue Engineering, Institute of Reconstructive Plastic Surgery, New York University, New York, New York, USA.
Tepper
Oren M
OM
Capla
Jennifer M
JM
Bhatt
Kirit A
KA
Ceradini
Daniel J
DJ
Galiano
Robert D
RD
Blei
Francine
F
Levine
Jamie P
JP
Gurtner
Geoffrey C
GC
D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34 / Q000096:biosynthesis*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002675:Child, Preschool; D005434:Flow Cytometry; D051272:Glucose Transporter Type 1; D006023:Glycoproteins / Q000096:biosynthesis*; D006391:Hemangioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007223:Infant; D007797:Laminin / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D009004:Monosaccharide Transport Proteins / Q000096:biosynthesis; D009360:Neoplastic Cells, Circulating; D010455:Peptides; D017452:Receptors, IgG / Q000096:biosynthesis; D013234:Stem Cells / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis
D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D051272:Glucose Transporter Type 1; D006023:Glycoproteins; D007797:Laminin; D009004:Monosaccharide Transport Proteins; C000606023:PROM1 protein, human; D010455:Peptides; D017452:Receptors, IgG; C495677:SLC2A1 protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2