Expression of VEGFR-2 and AC133 by circulating human CD34+ cells identifies a population of functional endothelial precursors

Blood - Tập 95 Số 3 - Trang 952-958 - 2000
Mario Peichev1, Afzal J. Naiyer1, Daniel Peixoto Pereira1, Zhenping Zhu1, William J. Lane1, Megan N. Williams1, Mehmet C. Öz1, Daniel J. Hicklin1, Luc de Witte1, Malcolm A.S. Moore1, Shahin Rafii1
1From the Division of Hematology-Oncology, Weill Medical College of Cornell University, New York, NY; Division of Molecular, Cell Biology and Immunology, ImClone Systems, New York, NY; Department of Cardiothoracic Surgery, Columbia-Presbyterian Medical Center, New York, NY; and Division of Developmental Hematopoiesis, Sloan Kettering Cancer Center, New York, NY.

Tóm tắt

Emerging data suggest that a subset of circulating human CD34+ cells have phenotypic features of endothelial cells. Whether these cells are sloughed mature endothelial cells or functional circulating endothelial precursors (CEPs) is not known. Using monoclonal antibodies (MoAbs) to the extracellular domain of the human vascular endothelial receptor-2 (VEGFR-2), we have shown that 1.2 ± 0.3% of CD34+ cells isolated from fetal liver (FL), 2 ± 0.5% from mobilized peripheral blood, and 1.4 ± 0.5% from cord blood were VEGFR-2+. In addition, most CD34+VEGFR-2+ cells express hematopoietic stem cell marker AC133. Because mature endothelial cells do not express AC133, coexpression of VEGFR-2 and AC133 on CD34+ cells phenotypically identifies a unique population of CEPs. CD34+VEGFR-2+ cells express endothelial-specific markers, including VE-cadherin and E-selectin. Also, virtually all CD34+VEGFR-2+ cells express the chemokine receptor CXCR4 and migrate in response to stromal-derived factor (SDF)-1 or VEGF. To quantitate the plating efficiency of CD34+ cells that give rise to endothelial colonies, CD34+ cells derived from FL were incubated with VEGF and fibroblast growth factor (FGF)-2. Subsequent isolation and plating of nonadherent FL-derived VEGFR-2+ cells with VEGF and FGF-2 resulted in differentiation of AC133+VEGFR-2+ cells into adherent AC133−VEGFR-2+Ac-LDL+(acetylated low-density lipoprotein) colonies (plating efficiency of 3%). In an in vivo human model, we have found that the neo-intima formed on the surface of left ventricular assist devices is colonized with AC133+VEGFR-2+ cells. These data suggest that circulating CD34+ cells expressing VEGFR-2 and AC133 constitute a phenotypically and functionally distinct population of circulating endothelial cells that may play a role in neo-angiogenesis.

Từ khóa


Tài liệu tham khảo

Rafii, 1995, Characterization of hematopoietic cells arising on the textured surface of left ventricular assist devices., Ann Thorac Surg., 60, 1627, 10.1016/0003-4975(95)00807-1

Shi, 1998, Evidence for circulating bone marrow-derived endothelial cells., Blood., 92, 362, 10.1182/blood.V92.2.362

Sbarbati, 1991, Immunologic detection of endothelial cells in human whole blood., Blood., 77, 764, 10.1182/blood.V77.4.764.764

Scott, 1994, The role of circulating cells in the healing of vascular prostheses., J Vasc Surg., 19, 585, 10.1016/S0741-5214(94)70030-3

Solovey, 1997, Circulating activated endothelial cells in sickle cell anemia., N Engl J Med., 337, 1584, 10.1056/NEJM199711273372203

Wu, 1995, Definitive proof of endothelialization of a Dacron arterial prosthesis in a human being., J Vasc Surg., 21, 862, 10.1016/S0741-5214(05)80019-9

Shi, 1994, Proof of fallout endothelialization of impervious Dacron grafts in the aorta and inferior vena cava of the dog., J Vasc Surg., 20, 546, 10.1016/0741-5214(94)90279-8

Coffin, 1991, Angioblast differentiation and morphogenesis of the vascular endothelium in the mouse embryo., Dev Biol., 148, 51, 10.1016/0012-1606(91)90316-U

Robert, 1996, Evidence that embryonic kidney cells expressing flk-1 are intrinsic, vasculogenic angioblasts., Am J Physiol., 271, F744

Caprioli, 1998, Blood-borne seeding by hematopoietic and endothelial precursors from the allantois., Proc Natl Acad Sci U S A., 95, 1641, 10.1073/pnas.95.4.1641

Flamme, 1995, Vascular endothelial growth factor (VEGF) and VEGF receptor 2 (flk-1) are expressed during vasculogenesis and vascular differentiation in the quail embryo., Dev Biol., 169, 699, 10.1006/dbio.1995.1180

Sato, 1993, Tie-1 and tie-2 define another class of putative receptor tyrosine kinase genes expressed in early embryonic vascular system [published erratum appears in Proc Natl Acad Sci U S A. 1993;90:12,056]., Proc Natl Acad Sci U S A., 90, 9355, 10.1073/pnas.90.20.9355

Sato, 1995, Distinct roles of the receptor tyrosine kinases Tie-1 and Tie-2 in blood vessel formation., Nature., 376, 70, 10.1038/376070a0

Schnurch, 1993, Expression of tie-2, a member of a novel family of receptor tyrosine kinases, in the endothelial cell lineage., Development., 119, 957, 10.1242/dev.119.3.957

Ali, 1997, Vascular endothelial cadherin (VE-cadherin): cloning and role in endothelial cell-cell adhesion., Microcirculation., 4, 267, 10.3109/10739689709146790

Vittet, 1996, Embryonic stem cells differentiate in vitro to endothelial cells through successive maturation steps., Blood., 88, 3424, 10.1182/blood.V88.9.3424.bloodjournal8893424

Asahara, 1997, Isolation of putative progenitor endothelial cells for angiogenesis., Science., 275, 964, 10.1126/science.275.5302.964

Miraglia, 1997, A novel five-transmembrane hematopoietic stem cell antigen: isolation, characterization, and molecular cloning., Blood., 90, 5013, 10.1182/blood.V90.12.5013

Yin, 1997, AC133, a novel marker for human hematopoietic stem and progenitor cells., Blood., 90, 5002, 10.1182/blood.V90.12.5002

Senger, 1996, Stimulation of endothelial cell migration by vascular permeability factor/vascular endothelial growth factor through cooperative mechanisms involving the alphavbeta3 integrin, osteopontin, and thrombin., Am J Pathol., 149, 293

Yoshida, 1996, Differential endothelial migration and proliferation to basic fibroblast growth factor and vascular endothelial growth factor., Growth Factors., 13, 57, 10.3109/08977199609034566

Rafii, 1994, Isolation and characterization of human bone marrow microvascular endothelial cells: hematopoietic progenitor cell adhesion., Blood., 84, 10, 10.1182/blood.V84.1.10.10

Gupta, 1998, Chemokine receptors in human endothelial cells: functional expression of CXCR4 and its transcriptional regulation by inflammatory cytokines., J Biol Chem., 273, 4282, 10.1074/jbc.273.7.4282

Feil, 1998, Endothelial cells differentially express functional CXC-chemokine receptor-4 (CXCR-4/fusin) under the control of autocrine activity and exogenous cytokines., Biochem Biophys Res Commun., 247, 38, 10.1006/bbrc.1998.8499

Tachibana, 1998, The chemokine receptor CXCR4 is essential for vascularization of the gastrointestinal tract., Nature., 393, 591, 10.1038/31261

Zou, 1998, Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development., Nature., 393, 595, 10.1038/31269

Auerbach, 1996, Hematopoietic stem cells in the mouse embryonic yolk sac., Stem Cells., 14, 269, 10.1002/stem.140269

Eichmann, 1997, Ligand-dependent development of the endothelial and hemopoietic lineages from embryonic mesodermal cells expressing vascular endothelial growth factor receptor 2., Proc Natl Acad Sci U S A., 94, 5141, 10.1073/pnas.94.10.5141

Shalaby, 1995, Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice., Nature., 376, 62, 10.1038/376062a0

Thông tin
Thông tin xuất bản

Blood

Tập 95 Số 3

952-958

Thông tin tác giả