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Prepublished online as a Blood First Edition Paper on September 19, 2002; DOI 10.1182/blood-2002-03-0711.
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Blood, 1 February 2003, Vol. 101, No. 3, pp. 869-876
HEMATOPOIESIS
Identification of a novel class of human adherent
CD34 stem cells that give rise to SCID-repopulating
cells
Selim Kuçi,
Johannes T. Wessels,
Hans-Jörg Bühring,
Karin Schilbach,
Michael Schumm,
Gabriele Seitz,
Jürgen Löffler,
Peter Bader,
Paul G. Schlegel,
Dietrich Niethammer, and
Rupert Handgretinger
From the Department of Hematology/Oncology, University
Children's Hospital, Tübingen, Germany; Division of
Hematology and Oncology, University Medical Clinic, Tübingen,
Germany; University Children's Hospital, Würzburg,
Germany; and the Division of Stem Cell Transplantation, St
Jude Children's Research Hospital, Memphis, TN.
Here we describe the in vitro generation of a novel adherent
cell fraction derived from highly enriched, mobilized
CD133+ peripheral blood cells after their culture with
Flt3/Flk2 ligand and interleukin-6 for 3 to 5 weeks. These cells lack
markers of hematopoietic stem cells, endothelial cells, mesenchymal
cells, dendritic cells, and stromal fibroblasts. However, all adherent cells expressed the adhesion molecules VE-cadherin, CD54, and CD44.
They were also positive for CD164 and CD172a (signal regulatory protein- ) and for a stem cell antigen defined by the recently described antibody W7C5. Adherent cells can either spontaneously or
upon stimulation with stem cell factor give rise to a
transplantable, nonadherent CD133+CD34
stem cell subset. These cells do not generate in vitro
hematopoietic colonies. However, their transplantation into
nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice
induced substantially higher long-term multilineage engraftment
compared with that of freshly isolated CD34+ cells,
suggesting that these cells are highly enriched in SCID-repopulating cells. In addition to cells of the myeloid lineage, nonadherent CD34 cells were able to give rise to human cells with B-,
T-, and natural killer-cell phenotype. Hence, these cells possess a
distinct in vivo differentiation potential compared with that of
CD34+ stem cells and may therefore provide an alternative
to CD34+ progenitor cells for transplantation.
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