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Endothelial progenitor cells and pregnancy

Published:August 26, 2008DOI:https://doi.org/10.1016/j.ajog.2008.06.041
      To the Editors:
      Savvidou et al
      • Savvidou M.D.
      • Xiao Q.
      • Kaihura C.
      • et al.
      Maternal circulating endothelial progenitor cells in normal singleton and twin pregnancy.
      reported a decline in endothelial progenitor cells (EPCs) in the maternal circulation with advancing gestation. The available literature on EPCs during pregnancy is conflicting, however, as appropriately acknowledged by the authors.
      The approach used by Savvidou et al was to culture unfractionated peripheral blood mononuclear cells (PBMCs) in supplemented endothelial growth media for 3 days, whereupon the nonadherent fraction of cells was removed, resulting in a fibronectin-adherent subpopulation. EPCs were enumerated as a percentage of the adhered PBMCs, according to double positivity for surface binding of the Ulex europeus agglutinin (lectin) and uptake of acetylated low-density lipoprotein. It should be noted, however, that the cells collected in this manner comprise as much as 2% of the whole PBMC population, are poorly proliferative, and display features of monocytes and macrophages throughout the culture period despite expression of endothelial markers.
      • Prater D.N.
      • Case J.
      • Ingram D.A.
      • Yoder M.C.
      Working hypothesis to redefine endothelial progenitor cells.
      • Zhang S.J.
      • Zhang H.
      • Wei Y.
      • et al.
      Adult endothelial progenitor cells from human peripheral blood maintain monocyte/macrophage function throughout in vitro culture.
      Although these circulating cells may be critically important to endothelial health, they are perhaps better described as proangiogenic myeloid cells or circulating angiogenic cells.
      • Prater D.N.
      • Case J.
      • Ingram D.A.
      • Yoder M.C.
      Working hypothesis to redefine endothelial progenitor cells.
      These cells often correlate poorly with EPCs enumerated on the basis of stem cell antigens (CD133 and/or CD34) in combination with vascular endothelial growth factor receptor-2. The latter subtype of EPC represents between 0.001% and 0.03% of total PBMCs from normal peripheral blood.
      • Prater D.N.
      • Case J.
      • Ingram D.A.
      • Yoder M.C.
      Working hypothesis to redefine endothelial progenitor cells.
      Other methodologies such as the colony-forming unit (Hill) assay and the late outgrowth assay select for different cells that are also referred to as EPCs.
      • Prater D.N.
      • Case J.
      • Ingram D.A.
      • Yoder M.C.
      Working hypothesis to redefine endothelial progenitor cells.
      Given this heterogeneity, it may be premature to conclude that normal pregnancy is associated with a progressive overall decline in maternal circulating EPCs. Nevertheless, the study by Savvidou et al is informative and should stimulate further investigation regarding the role of EPCs in normal and abnormal pregnancy.

      References

        • Savvidou M.D.
        • Xiao Q.
        • Kaihura C.
        • et al.
        Maternal circulating endothelial progenitor cells in normal singleton and twin pregnancy.
        Am J Obstet Gynecol. 2008; 198: 414.e1-414.e5
        • Prater D.N.
        • Case J.
        • Ingram D.A.
        • Yoder M.C.
        Working hypothesis to redefine endothelial progenitor cells.
        Leukemia. 2007; 21: 1141-1149
        • Zhang S.J.
        • Zhang H.
        • Wei Y.
        • et al.
        Adult endothelial progenitor cells from human peripheral blood maintain monocyte/macrophage function throughout in vitro culture.
        Cell Res. 2006; 16: 577-584

      Linked Article

      • Maternal circulating endothelial progenitor cells in normal singleton and twin pregnancy
        American Journal of Obstetrics & GynecologyVol. 198Issue 4
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          The objective of the study was to determine the levels of circulating endothelial progenitor cells (EPCs), which are peripheral blood mononuclear cells (PBMNCs) that contribute to vascular repair in normal pregnancy.
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        American Journal of Obstetrics & GynecologyVol. 200Issue 1
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          We thank Dr Hubel for his comments. The methodology to identify circulating endothelial progenitor cells (EPCs) used in our study has been described in detail.1 In many previous studies, EPCs are described as a peripheral blood mononuclear cell (PBMC) population expressing CD34, kinase insert domain receptor (KDR)/vascular endothelial growth factor receptor-2, and CD133/AC133 with adherent growth characteristics.
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