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Blood, 1 May 2002, Vol. 99, No. 9, pp. 3454-3457
BRIEF REPORT
Ex vivo treatment of proliferating human cord blood stem cells
with stroma-derived factor-1 enhances their ability to engraft
NOD/SCID mice
Hanno Glimm,
Patrick Tang,
Ian Clark-Lewis,
Christof von Kalle, and
Connie Eaves
From the Terry Fox Laboratory, British Columbia Cancer
Agency, and the Departments of Biochemistry and Medical Genetics and
the Biomedical Research Centre, University of British Columbia,
Vancouver, Canada; and Department I of Internal Medicine and Institute
for Molecular Medicine and Cell Research, University of Freiburg,
Germany.
Ex vivo proliferation of hematopoietic stem cells (HSCs) is
important for cellular and gene therapy but is limited by the observation that HSCs do not engraft as they transit
S/G2/M. Recently identified candidate inhibitors of human
HSC cycling are transforming growth factor- 1
(TGF-1) and stroma-derived factor-1 (SDF-1). To
determine the ability of these factors to alter the transplantability of human HSCs proliferating in vitro, lin cord blood
cells were first cultured for 96 hours in serum-free medium containing
Flt3 ligand, Steel factor, interleukin-3, interleukin-6, and
granulocyte colony-stimulating factor. These cells were then transferred to medium containing Steel factor and thrombopoietin with
or without SDF-1 and/or TGF-1 for 48 hours. Exposure to SDF-1 but not TGF-1 significantly increased (> 2-fold)
the recovery of HSCs able to repopulate nonobese diabetic/severe
combined immunodeficiency mice. These results suggest new strategies
for improving the engraftment activity of HSCs stimulated to
proliferate ex vivo.
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