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Blood, 15 September 2000, Vol. 96, No. 6, pp. 2100-2107
HEMATOPOIESIS
Similar repopulating capacity of mitotically active and resting
umbilical cord blood CD34+ cells in
NOD/SCID mice
Jannine Wilpshaar,
J. H. Frederik Falkenburg,
Xia Tong,
Willy A. Noort,
Robert Breese,
Doug Heilman,
Humphrey Kanhai,
Christie M. Orschell-Traycoff, and
Edward F. Srour
From the Departments of Hematology and
Obstetrics, Leiden University Medical Center, Leiden, The Netherlands;
and the Division of Hematology/Oncology, Department of Medicine;
Department of Pediatrics, Herman B Wells Center for Pediatric Research;
Department of Biostatistics; and the Department of
Microbiology/Immunology; Indiana University School of Medicine,
Indianapolis, IN.
It was hypothesized that during mammalian development, the
extensive need for hematopoietic cells requires equal contribution to
blood cell production from both quiescent and cycling hematopoietic stem cells (HSCs) while maintaining the stem cell pool. To investigate this hypothesis, the engraftment potential of umbilical cord blood (UCB) CD34+ cells residing in either G0
(G0CD34+ cells) or G1
(G1CD34+ cells) phases of the cell cycle was
assessed in nonobese diabetic/severe combined immune-deficient
(NOD/SCID) mice. Whereas the level of chimerism in mice
transplanted with UCB G0CD34+ cells was
69.9% ± 24.0%, mice receiving equal numbers of
G1CD34+ cells harbored 46.7% ± 21.3% human
cells 8 weeks posttransplantation. Both groups of cells sustained
multilineage differentiation and the production of CD34+
cells in recipient animals. The relationship between the number of
transplanted G0CD34+ or
G1CD34+ cells and the level of chimerism was
analyzed by a general linear models procedure. Although the initial
level of chimerism following transplantation of
G0CD34+ cells was higher than that sustained by
G1CD34+ cells, the increment in the degree of
chimerism obtained with each additional 103 cells of either
phenotype was identical, suggesting that the reconstitution potential
of these 2 types of cells was similar. Of interest is that human cells
recovered from primary recipients of both
G0CD34+ and G1CD34+
cells engrafted in secondary NOD/SCID recipients, albeit at a substantially lower level, confirming the primitive nature of UCB
CD34+ cells residing in G1.
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