CD34+/CD133- circulating endothelial precursor cells (CEP): characterization, senescence and in vivo application.
Circulating endothelial precursor cells (CEP) are interesting candidates for the treatment of ischemic diseases and for tumor targeting/imaging. We isolated a homogeneous population of CEP from CD34(+)/CD133(-) cells of peripheral blood that can be expanded easily on collagen-type-I coated plastic. CEP displayed a phenotype of mature endothelial cells (vWF, CD31, CD34, VEGF-R2, CD105, CD146) similar to that of cord-blood CEP and umbilical vein endothelial cells. They bound UEA-1 lectin, incorporated acetylated LDL and formed tube-like structures with capillary lumens in vitro. Weibel-Palade bodies were observed by electron microscopy. After 40-60 cell population doublings, CEP cultures underwent a terminal growth arrest, had shorter telomeres, up-regulated cell cycle inhibitory proteins, such as p21(CIP1) and stained positive for senescence-associated-beta galactosidase. During the whole expansion period CEP retained their endothelial phenotype and a normal karyotype. CEP had the capacity to home to ischemic tissue in vivo after systemic injection in nude rats. The convenient expandability, the homogenous phenotype, the functional cellular senescence program, the regular karyotype and the homing capacity to ischemic myocardium suggest autologous CEP cultures as a safe and promising tool for cell-based therapeutic approaches in targeting ischemic tissue and tumors.
Untergasser
Gerold
G
Tumor Biology and Angiogenesis Laboratory, Division of Haematology and Oncology, Innsbruck Medical University, Innsbruck, Austria. gerold.untergasser@uibk.ac.at
Koeck
Ruth
R
Wolf
Dominik
D
Rumpold
Holger
H
Ott
Harald
H
Debbage
Paul
P
Koppelstaetter
Christian
C
Gunsilius
Eberhard
E
D000071916:AC133 Antigen; D000328:Adult; D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D018952:Antigens, CD34 / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D016922:Cellular Senescence / Q000502:physiology*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000502:physiology; D042783:Endothelial Cells / Q000166:cytology* / Q000276:immunology; D006023:Glycoproteins / Q000502:physiology*; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000276:immunology; D008875:Middle Aged; D023421:Models, Animal; D017202:Myocardial Ischemia / Q000473:pathology; D010455:Peptides / Q000502:physiology*; D010641:Phenotype; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000502:physiology; D051381:Rats; D011923:Rats, Nude; D014841:von Willebrand Factor / Q000502:physiology
D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D050759:Cyclin-Dependent Kinase Inhibitor p21; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D019408:Platelet Endothelial Cell Adhesion Molecule-1; C000606025:Prom1 protein, rat; D014841:von Willebrand Factor