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A functional comparison of CD34 + CD38- cells in cord blood and bone marrow

QL Hao, AJ Shah, FT Thiemann, EM Smogorzewska and GM Crooks

Division of Research Immunology and Bone Marrow Transplantation, Childrens Hospital Los Angeles, CA 90027, USA.

We present cell cycling and functional evidence that the CD34+CD38- immunophenotype can be used to define a rare and primitive subpopulation of progenitor cells in umbilical cord blood. CD34+CD38- cells comprise 0.05% +/- 0.08% of the mononuclear cells present in cord blood. Cell cycle analysis with the fluorescent DNA stain 7- aminoactinomycin D showed that the percentage of CD34+ cells in cycle directly correlated with increasing CD38 expression. CD34+CD38- cord blood cells were enriched for long-term culture-initiating cells (LTCIC; cells able to generate colony-forming unit-cells [CFU-C] after 35 to 60 days of coculture with bone marrow stroma) relative to CD34+CD38- cells. In an extended LTCIC assay, CD34+CD38- cells were able to generate CFU-C between days 60 and 100, clearly distinguishing them from CD34+CD38+ cells that did not generate CFU-C beyond day 40. When plated as single cells, onset of clonal proliferation was markedly delayed in a subpopulation of CD34+CD38- cells; clones (defined as > 100 cells) appeared after 60 days of culture in 2.9% of CD34+CD38- cells. In contrast, 100% of CD34+CD38+ cells formed clones by day 21. Although the CD34+CD38- immunophenotype defines highly primitive populations in both bone marrow and cord blood, important functional differences exist between the two sources. CD34+CD38- cord blood cells have a higher cloning efficiency, proliferate more rapidly in response to cytokine stimulation, and generate approximately sevenfold more progeny than do their counterparts in bone marrow.

Volume 86, Issue 10, pp. 3745-3753, 11/15/1995
Copyright © 1995 by The American Society of Hematology


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K. P. Schofield, G. Rushton, M. J. Humphries, T. M. Dexter, and J. T. Gallagher
Influence of Interleukin-3 and Other Growth Factors on alpha 4beta 1 Integrin-Mediated Adhesion and Migration of Human Hematopoietic Progenitor Cells
Blood, September 1, 1997; 90(5): 1858 - 1866.
[Abstract] [Full Text] [PDF]


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JEMHome page
M. Bhatia, D. Bonnet, U. Kapp, J. C.Y. Wang, B. Murdoch, and J. E. Dick
Quantitative Analysis Reveals Expansion of Human Hematopoietic Repopulating Cells After Short-term Ex Vivo Culture
J. Exp. Med., August 18, 1997; 186(4): 619 - 624.
[Abstract] [Full Text] [PDF]


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O. I. Gan, B. Murdoch, A. Larochelle, and J. E. Dick
Differential Maintenance of Primitive Human SCID-Repopulating Cells, Clonogenic Progenitors, and Long-Term Culture-Initiating Cells After Incubation on Human Bone Marrow Stromal Cells
Blood, July 15, 1997; 90(2): 641 - 650.
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J. C.Y. Wang, M. Doedens, and J. E. Dick
Primitive Human Hematopoietic Cells Are Enriched in Cord Blood Compared With Adult Bone Marrow or Mobilized Peripheral Blood as Measured by the Quantitative In Vivo SCID-Repopulating Cell Assay
Blood, June 1, 1997; 89(11): 3919 - 3924.
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Proc. Natl. Acad. Sci. USAHome page
M. Bhatia, J. C. Y. Wang, U. Kapp, D. Bonnet, and J. E. Dick
Purification of primitive human hematopoietic cells capable of repopulating immune-deficient mice
PNAS, May 13, 1997; 94(10): 5320 - 5325.
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W. Piacibello, F. Sanavio, L. Garetto, A. Severino, D. Bergandi, J. Ferrario, F. Fagioli, M. Berger, and M. Aglietta
Extensive Amplification and Self-Renewal of Human Primitive Hematopoietic Stem Cells From Cord Blood
Blood, April 15, 1997; 89(8): 2644 - 2653.
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M. A. Dao, C. H. Hannum, D. B. Kohn, and J. A. Nolta
FLT3 Ligand Preserves the Ability of Human CD34+ Progenitors to Sustain Long-Term Hematopoiesis in Immune-Deficient Mice After Ex Vivo Retroviral-Mediated Transduction
Blood, January 15, 1997; 89(2): 446 - 456.
[Abstract] [Full Text] [PDF]



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