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Blood, 1 July 2002, Vol. 100, No. 1, pp. 120-127
HEMATOPOIESIS
Engraftment potential of human fetal hematopoietic cells in
NOD/SCID mice is not restricted to mitotically quiescent
cells
Jannine Wilpshaar,
Mickie Bhatia,
Humphrey H. H. Kanhai,
Robert Breese,
Doug K. Heilman,
Cynthia S. Johnson,
J. H. Frederik Falkenburg, and
Edward F. Srour
From the Departments of Hematology and Obstetrics,
Leiden University Medical Center, The Netherlands; Developmental Stem
Cell Biology, Robarts Research Institute, London, Ontario, Canada; and
Department of Pediatrics/Herman B. Wells Center for Pediatric Research,
Department of Biostatistics/Division of Hematology/Oncology, Department
of Medicine, and Department of Microbiology/Immunology, Indiana
University School of Medicine, Indianapolis, IN.
During fetal development, there is a continued demand for large
numbers of primitive and mature hematopoietic cells. This demand may
require that all potential hematopoietic stem cells (HSCs) migrate
effectively to emerging hematopoietic sites and subsequently contribute
to blood cell production, regardless of their cell cycle status. We
recently established that umbilical cord blood cells in the
G1 phase of the cell cycle have a repopulating potential
similar to cells in G0, suggesting that cycling prenatal and neonatal HSCs may have the same functional capabilities described for quiescent, but not cycling, cells from adult sources. To establish the relationship between cell cycle status and hematopoietic potential at early stages of human ontogeny, the in vivo engraftment potential of
mitotically defined fetal liver (FL) and fetal bone marrow (FBM) cells
were examined in NOD/SCID recipients. Following transplantation of the
same numbers of G0, G1, or S/G2+M
CD34+ cells from FL, equivalent percentages of recipient
mice were chimeric (55%, 60%, and 60%, respectively). FBM-derived
CD34+ cells in all phases of the cell cycle engrafted in
conditioned recipients and sustained human hematopoiesis, albeit at
lower levels than their FL-derived counterparts. Multilineage
differentiation was evident in all transplanted mice independent of the
source or cell cycle status of graft cells. In addition, levels of
chimerism in mice transplanted with fetal blood-derived G0
or G1 CD34+ lineage-depleted cells were
similar. These results support the assertion that mitotically quiescent
and cycling fetal hematopoietic cells contain marrow-repopulating stem
cells capable of multilineage engraftment in NOD/SCID mouse recipients.
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