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 g...

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Veröffentlicht in:Journal of cellular and molecular medicine 2009-03, Vol.13 (3), p.522-534
Hauptverfasser: Nguyen, Van Anh, Fürhapter, Christina, Obexer, Petra, Stössel, Hella, Romani, Nikolaus, Sepp, Norbert
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container_issue 3
container_start_page 522
container_title Journal of cellular and molecular medicine
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creator Nguyen, Van Anh
Fürhapter, Christina
Obexer, Petra
Stössel, Hella
Romani, Nikolaus
Sepp, Norbert
description 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‐α, 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.
doi_str_mv 10.1111/j.1582-4934.2008.00340.x
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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‐α, 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. 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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‐α, 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. 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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‐α, 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.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>18410526</pmid><doi>10.1111/j.1582-4934.2008.00340.x</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record>
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subjects AC133 Antigen
Adenosine
Angiogenesis
Antibodies
Antigens, CD - metabolism
Antigens, CD34 - metabolism
Blood
Blood vessels
Cardiovascular disease
CD105 antigen
CD34 antigen
CD36 antigen
Cell adhesion & migration
Cell adhesion molecules
Cell culture
Cell cycle
Cell Differentiation
Cell Shape
Cell therapy
Cells, Cultured
Child
Child, Preschool
Cord blood
Cytokines
DNA microarrays
Down-Regulation
Electron microscopy
Endoglin
endothelial cell differentiation
Endothelial cells
Endothelial Cells - cytology
Endothelial Cells - metabolism
Endothelial Cells - ultrastructure
Endothelium
Epidermal growth factor
Extracellular matrix
Fetal Blood - cytology
Flow cytometry
Gene expression
Gene Expression Profiling
Glycoproteins - metabolism
Hematopoietic stem cells
Hemopoiesis
Humans
Infant
Infant, Newborn
Intercellular adhesion molecule 1
lymphatic capillaries
Lymphatic system
Lymphatic Vessels - cytology
Magnetic fields
Male
Morphology
Oligonucleotide Array Sequence Analysis
Penicillin
Peptides - metabolism
Phenotype
Progenitor cells
stem cells
Stem Cells - cytology
Stem Cells - metabolism
Stem Cells - ultrastructure
Tumor necrosis factor-α
Umbilical cord
Umbilical vein
Up-Regulation
Vascular endothelial growth factor
Vascular endothelial growth factor receptor 2
Vascular endothelial growth factor receptors
Vascularization
vasculogenesis
Weibel-Palade Bodies - ultrastructure
title Endothelial cells from cord blood CD133+CD34+ progenitors share phenotypic, functional and gene expression profile similarities with lymphatics
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