Endothelial cells from cord blood CD133+CD34+ progenitors share phenotypic, functional and gene expression profile similarities with lymphatics.
The existence of endothelial progenitor cells (EPC) with high cell-cycle rate in human umbilical cord blood has been recently shown and represents a challenging strategy for therapeutic neovascularization. To enhance knowledge for future cellular therapy, we compared the phenotypic, functional and gene expression differences between EPC-derived cells generated from cord blood CD34(+) cells, and lymphatic and macrovascular endothelial cells (EC) isolated from human foreskins and umbilical veins, respectively. Under appropriate culture conditions, EPC developed into fully matured EC with expression of similar endothelial markers as lymphatic and macrovascular EC, including CD31, CD36, von Willebrand factor FVIII, CD54 (ICAM-1), CD105 (endoglin), CD144 (VE-cadherin), Tie-1, Tie-2, VEGFR-1/Flt-1 and VEGFR-2/Flk-1. Few EPC-derived cells became positive for LYVE-1, indicating their origin from haematopoietic stem cells. However they lacked expression of other lymphatic cell-specific markers such as podoplanin and Prox-1. Functional tests demonstrated that the cobblestone EPC-derived cells up-regulated CD54 and CD62E expression in response to TNF-alpha, incorporated DiI-acetylated low-density liproprotein and formed cord- and tubular-like structures with capillary lumen in three-dimensional collagen culture--all characteristic features of the vascular endothelium. Structures compatible with Weibel-Palade bodies were also found by electron microscopy. Gene microarray profiling revealed that only a small percentage of genes investigated showed differential expression in EPC-derived cells and lymphatic EC. Among them were adhesion molecules, extracellular matrix proteins and cytokines. Our data point to the close lineage relationship of both types of vascular cells and support the theory of a venous origin of the lymphatic system.
Nguyen
Van Anh
VA
Department of Dermatology, Innsbruck Medical University, Innsbruck, Austria. van.nguyen@i-med.ac.at
Fürhapter
Christina
C
Obexer
Petra
P
Stössel
Hella
H
Romani
Nikolaus
N
Sepp
Norbert
N
D000071916:AC133 Antigen; D015703:Antigens, CD / Q000378:metabolism*; D018952:Antigens, CD34 / Q000378:metabolism*; D002454:Cell Differentiation; D048430:Cell Shape; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D015536:Down-Regulation; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism* / Q000648:ultrastructure; D005312:Fetal Blood / Q000166:cytology; D020869:Gene Expression Profiling; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D042601:Lymphatic Vessels / Q000166:cytology*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010455:Peptides / Q000378:metabolism*; D010641:Phenotype; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D015854:Up-Regulation; D020302:Weibel-Palade Bodies / Q000648:ultrastructure
D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides