Title | VEGFR-3 and CD133 identify a population of CD34+ lymphatic/vascular endothelial precursor cells. |
Publication Type | Journal Article |
Year of Publication | 2003 |
Authors | Salven P, Mustjoki S, Alitalo R, Alitalo K, Rafii S |
Journal | Blood |
Volume | 101 |
Issue | 1 |
Pagination | 168-72 |
Date Published | 2003 Jan 01 |
ISSN | 0006-4971 |
Keywords | AC133 Antigen, Antigens, CD, Antigens, CD34, Blood Cells, Cell Culture Techniques, Cell Division, Endothelium, Lymphatic, Endothelium, Vascular, Fetal Blood, Fetus, Glycoproteins, Humans, Immunophenotyping, Liver, Peptides, RNA, Messenger, Stem Cells, Vascular Endothelial Growth Factor Receptor-3 |
Abstract | Human CD133 (AC133)(+)CD34(+) stem and progenitor cells derived from fetal liver and from bone marrow and blood incorporate a functional population of circulating endothelial precursor cells. Vascular endothelial growth factor receptor 3 (VEGFR-3) regulates cardiovascular development and physiological and pathological lymphangiogenesis and angiogenesis. However, the origin of VEGFR-3(+) endothelial cells (ECs) and the mechanisms by which these cells contribute to postnatal physiological processes are not known, and the possible existence of VEGFR-3(+) lymphatic or vascular EC progenitors has not been studied. Using monoclonal antibodies to the extracellular domain of VEGFR-3, we show that 11% +/- 1% of CD34(+) cells isolated from human fetal liver, 1.9% +/- 0.8% CD34(+) cells from human cord blood, and 0.2% +/- 0.1% of CD34(+) cells from healthy adult blood donors are positive for VEGFR-3. CD34(+)VEGFR-3(+) cells from fetal liver coexpress the stem/precursor cell marker CD133 (AC133). Because mature ECs do not express CD133, coexpression of VEGFR-3 and CD133 on CD34(+) cells identifies a unique population of stem and progenitor cells. Incubation of isolated CD34(+)VEGFR-3(+) cells in EC growth medium resulted in a strong proliferation (40-fold in 2 weeks) of nonadherent VEGFR-3(+) cells. Plating of these cells resulted in the formation of adherent VEGFR-3(+)Ac-LDL(+) (Ac-LDL = acetylated low-density lipoprotein) EC monolayers expressing various vascular and lymphatic endothelial-specific surface markers, including CD34, VE-cadherin, CD51/61, CD105, LYVE-1, and podoplanin. These data demonstrate that human CD34(+)CD133(+) cells expressing VEGFR-3 constitute a phenotypically and functionally distinct population of endothelial stem and precursor cells that may play a role in postnatal lymphangiogenesis and/or angiogenesis. |
DOI | 10.1182/blood-2002-03-0755 |
Alternate Journal | Blood |
PubMed ID | 12393704 |