Origin of endothelial progenitors in human postnatal bone marrow.
This study demonstrates that a CD34(-), vascular endothelial cadherin(-) (VE-cadherin(-)), AC133(+), and fetal liver kinase(+) (Flk1(+)) multipotent adult progenitor cell (MAPC) that copurifies with mesenchymal stem cells from postnatal human bone marrow (BM) is a progenitor for angioblasts. In vitro, MAPCs cultured with VEGF differentiate into CD34(+), VE-cadherin(+), Flk1(+) cells - a phenotype that would be expected for angioblasts. They subsequently differentiate into cells that express endothelial markers, function in vitro as mature endothelial cells, and contribute to neoangiogenesis in vivo during tumor angiogenesis and wound healing. This in vitro model of preangioblast-to-endothelium differentiation should prove very useful in studying commitment to the angioblast and beyond. In vivo, MAPCs can differentiate in response to local cues into endothelial cells that contribute to neoangiogenesis in tumors. Because MAPCs can be expanded in culture without obvious senescence for more than 80 population doublings, they may be an important source of endothelial cells for cellular pro- or anti-angiogenic therapies.
Reyes
Morayma
M
Stem Cell Institute, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
Dudek
Arkadiusz
A
Jahagirdar
Balkrishna
B
Koodie
Lisa
L
Marker
Paul H
PH
Verfaillie
Catherine M
CM
D000071916:AC133 Antigen; D000293:Adolescent; D000328:Adult; D015703:Antigens, CD; D018952:Antigens, CD34 / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002454:Cell Differentiation; D002648:Child; D002675:Child, Preschool; D004730:Endothelium, Vascular / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D009369:Neoplasms / Q000098:blood supply; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic; D010455:Peptides / Q000378:metabolism; D010641:Phenotype; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor; D000099152:Cadherin 5
D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D015820:Cadherins; D006023:Glycoproteins; D010455:Peptides; D020794:Receptor Protein-Tyrosine Kinases; D017978:Receptors, Growth Factor; D040262:Receptors, Vascular Endothelial Growth Factor; D000099152:Cadherin 5; C000606023:PROM1 protein, human