[Vasculogenic potential of endothelial progenitor cells derived from human umbilical cord blood and their roles in neovascularization of malignant glioma].
OBJECTIVE
To investigate vasculogenic potential of endothelial progenitor cells (EPCs) derived from human umbilical cord blood and their contribution to the neovascularization of malignant glioma in vivo.


METHODS
EPCs were isolated from human umbilical cord blood by density gradient centrifugation. After 7-10 days of culture, EPCs were investigated for CD34 and VEGFR-2 expression by direct immunofluoresent staining. The proliferative activity, migratory capability and forming capillary-like tubules were also monitored after stimulation with VEGF(50 mg/L) in vitro. Moreover, EPCs were administered into tumor-bearing mice, and the tumor and mouse organs were examined under confocal laser scanning microscope to visualize the distribution and localization of transplanted EPCs. In order to quantity the incorporation of EPCs into tumor vessels, cryosections of the tumor tissue were double-labelled with antihuman CD31 and anti-mouse CD31.


RESULTS
After 7 to 10 days of culture, EPCs assumed cobblestone-like monolayer growth pattern with nearly complete confluence, and expressed CD34 and VEGFR-2. Significant proliferative activity, increased migratory capability and forming capillary-like tubules were observed when stimulated with VEGF. The transplanted EPCs in vivo specifically homed to solid tumor tissue and incorporated into the tumor's endothelium. Quantitative analysis revealed that human EPCs contributed significantly to tumor neovascularization by incorporation into tumor vasculature (18.68 +/- 1.32)% of the total vessels.


CONCLUSIONS
EPCs possess the potential to form neovascular network in tumor and play a role in the phenotypical heterogeneity of tumor microvascular architecture.
Institute of Pathology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
Hua-Rong
HR
Zhang
Fei-Lan
FL
Chen
Cheng-Ping
CP
Xu
Xiu-Wu
XW
Bian
D000818:Animals; D018952:Antigens, CD34 / Q000276:immunology; D042783:Endothelial Cells / Q000473:pathology* / Q000502:physiology; D004730:Endothelium, Vascular / Q000473:pathology* / Q000503:physiopathology; D005312:Fetal Blood / Q000166:cytology; D005910:Glioma / Q000150:complications* / Q000473:pathology; D006801:Humans; D051379:Mice; D009389:Neovascularization, Pathologic / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000276:immunology; D013234:Stem Cells / Q000473:pathology* / Q000502:physiology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000276:immunology
D018952:Antigens, CD34; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D040301:Vascular Endothelial Growth Factor Receptor-2