Endothelial progenitor cells from infantile hemangioma and umbilical cord blood display unique cellular responses to endostatin

Infantile hemanglomas are composed of endothelial cells (ECs), endothelial progenitor cells (EPCs), as well as perivascular and hematopoletic cells. Our hypothesis is that hemangioma-derived EPCs (HemEPCs) differentiate into the mature ECs that comprise the major compartment of the tumor. To test this, we isolated EPCs (CD133(+)/U/ex europeus-l+) anti mature ECs (CD133(-)lUiex europeus1(+)) from proliferating hemanglomas and used a previously described property of heinangioma-derived ECs (HemECs), enhanced migratory activity in response to the angiogenesis inhibitor endostatin, to determine if HemEPCs share this abnormal behavior. Umbilical cord bloodderived EPCs (cbEPCs) were analyzed in parallel as a normal control. Our results show that HemEPCs, HemECs, and cbEPCs exhibit increased adhesion, migration, and proliferation in response to endostatin. This angiogenic response to endostatin was consistently expressed by HemEPCs over several weeks in culture, whereas HemECs and cbEPCs shifted toward the mature endothelial re-expression patterns among HemEPCs, HemECs, and cbEPCs, revealed by microarray analyses, provided further indication of an EPC phenotype. This is the first demonstration that human EPCs, isolated from blood or from a proliferating hemangloma, are stimulated by an anglogenesis inhibitor. These findings suggest that EPCs respond differently from mature ECs when exposed to anglogenic or antlangiogenic signals. sponse to endostatin. Similar mRNA-expression patterns among HemEPCs, HemECs, and cbEPCs, revealed by microarray analyses, provided further indication of an EPC phenotype. This is the first demonstration that human EPCs, isolated from blood or from a proliferating hemangloma, are stimulated by an anglogenesis inhibitor. These findings suggest that EPCs respond differently from mature ECs when exposed to anglogenic or antlangiogenic signals.