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Cell-Surface Antigen Expression in Early and Term Gestation Fetal Hematopoietic Progenitor Cells

^a University of Washington School of Medicine;
^b Division of Perinatal Medicine, Department of Obstetrics and Gynecology, University of Washington, Seattle, Washington, USA;
^c Pediatric Hematology/Oncology, University of Washington School of Medicine and Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

Key Words. Fetal blood • Umbilical cord blood • CD34 • Stem cell

Correspondence: Dr. Laurence E. Shields, Department of Obstetrics and Gynecology, Division of Perinatal Medicine, Box 356460, University of Washington, Seattle, WA 98195-6460, USA.

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.

This article has been cited by other articles:

				L. E. Shields, L. K. Gaur, M. Gough, J. Potter, A. Sieverkropp, and R. G. Andrews In Utero Hematopoietic Stem Cell Transplantation in Nonhuman Primates: The Role of T Cells Stem Cells, May 1, 2003; 21(3): 304 - 314. [Abstract] [Full Text] [PDF]