In vitro differentiation of endothelial cells from AC133-positive progenitor cells

Author:

Gehling Ursula M.1,Ergün Süleyman1,Schumacher Udo1,Wagener Christoph1,Pantel Klaus1,Otte Marcus1,Schuch Gunter1,Schafhausen Philippe1,Mende Thorsten1,Kilic Nerbil1,Kluge Katrin1,Schäfer Birgit1,Hossfeld Dieter K.1,Fiedler Walter1

Affiliation:

1. From the Department of Hematology/Oncology, Department of Anatomy, Department of Neuroanatomy, Department of Clinical Chemistry, and Department of Gynecology, University Hospital Eppendorf, Hamburg, Germany.

Abstract

Recent findings support the hypothesis that the CD34+-cell population in bone marrow and peripheral blood contains hematopoietic and endothelial progenitor and stem cells. In this study, we report that human AC133+ cells from granulocyte colony-stimulating factor–mobilized peripheral blood have the capacity to differentiate into endothelial cells (ECs). When cultured in the presence of vascular endothelial growth factor (VEGF) and the novel cytokine stem cell growth factor (SCGF), AC133+ progenitors generate both adherent and proliferating nonadherent cells. Phenotypic analysis of the cells within the adherent population reveals that the majority display endothelial features, including the expression of KDR, Tie-2, Ulexeuropaeus agglutinin-1, and von Willebrand factor. Electron microscopic studies of these cells show structures compatible with Weibel-Palade bodies that are found exclusively in vascular endothelium. AC133-derived nonadherent cells give rise to both hematopoietic and endothelial colonies in semisolid medium. On transfer to fresh liquid culture with VEGF and SCGF, nonadherent cells again produce an adherent and a nonadherent population. In mice with severe combined immunodeficiency, AC133-derived cells form new blood vessels in vivo when injected subcutaneously together with A549 lung cancer cells. These data indicate that the AC133+-cell population consists of progenitor and stem cells not only with hematopoietic potential but also with the capacity to differentiate into ECs. Whether these hematopoietic and endothelial progenitors develop from a common precursor, the hemangioblast will be studied at the single-cell level.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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