In:
Blood, American Society of Hematology, Vol. 101, No. 1 ( 2003-01-01), p. 168-172
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.
Type of Medium:
Online Resource
ISSN:
1528-0020
,
0006-4971
DOI:
10.1182/blood-2002-03-0755
Language:
English
Publisher:
American Society of Hematology
Publication Date:
2003
detail.hit.zdb_id:
1468538-3
detail.hit.zdb_id:
80069-7
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