Cell-surface antigen expression in early and term gestation fetal hematopoietic progenitor cells.
The objective of this study was to compare the expression of primitive cell-surface antigens on CD34+ cells from early in gestation to those from term gestations. Fetal blood samples were obtained from 10 early gestation (21.0+/-0.8 [SE] weeks) and 12 term gestation (39.3+/-0.4 weeks) fetuses. The mononuclear cell population was separated by red cell lysis. Two-color flow cytometry was used to assess cell surface antigen coexpression of CD34 with CD33, CD38, and HLA-DR as well as staining by a cocktail of monoclonal antibodies for lineage-associated (Lin) antigens (CD2, CD10, CD11b, CD19, CD20, CD33, CD36, 7B9, and Glycophorin-A). The frequency of CD34+ cells (5.5+/-0.9 versus 1.5+/-0.2, p < 0.001) was significantly higher in the early gestational age group. Within the CD34+ population, the frequency of CD34+/CD38- cells (81.8+/-9.9 versus 51.3+/-7.7, p = 0.02) and CD34+/DR- cells (15.3+/-7.4 versus 8.2+/-2.7, p = 0.05) was also higher in the early gestational age group. In contrast, CD34+/CD33- (51.8+/-10.1 versus 83.0+/-6.1, p = 0.02) and CD34+/Lin- cells (15.9+/-7.0 versus 51.8 +/-6.9, p < 0.01) were higher in the term gestation group. The high percentage of CD34+, CD34+/CD38-, and CD34+/DR- cells supports our hypothesis that early gestational age fetal blood has a higher frequency of primitive hematopoietic progenitor/stem cells than does umbilical cord blood at term. This suggests that hematopoietic progenitor/stem cells in early fetal blood may be a desirable target for in utero gene therapy. However, further studies to characterize the functional properties of CD34+ cell subsets at different stages of fetal development will be necessary to determine the appropriateness of targeting fetal hematopoietic cells for in utero gene therapy. The higher frequency of CD34+/CD33- and CD34+/Lin- cells from term gestational age fetuses was unexpected, and the significance of this finding is unclear at this time.
Opie
T M
TM
University of Washington School of Medicine, Seattle, USA.
Shields
L E
LE
Andrews
R G
RG
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000029:Abortion, Legal; D015703:Antigens, CD / Q000032:analysis* / Q000096:biosynthesis*; D000943:Antigens, Differentiation / Q000032:analysis / Q000096:biosynthesis; D018955:CD36 Antigens / Q000032:analysis / Q000096:biosynthesis; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D005434:Flow Cytometry; D005865:Gestational Age; D006021:Glycophorins / Q000032:analysis / Q000096:biosynthesis; D006684:HLA-DR Antigens / Q000032:analysis / Q000096:biosynthesis; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000032:analysis / Q000096:biosynthesis; D009244:NAD+ Nucleosidase / Q000032:analysis / Q000096:biosynthesis; D011247:Pregnancy
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018955:CD36 Antigens; D006021:Glycophorins; D006684:HLA-DR Antigens; D008562:Membrane Glycoproteins; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1