Journal
BLOOD
Volume 99, Issue 9, Pages 3454-3457Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood.V99.9.3454
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Funding
- NHLBI NIH HHS [P01 HL-55435] Funding Source: Medline
- NIDDK NIH HHS [DKS7199] Funding Source: Medline
- PHS HHS [R01 A130389] Funding Source: Medline
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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/G(2)/M. Recently Identified candidate Inhibitors of human HSC cycling are transforming growth factor-beta(1) (TGF-beta(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, lincord blood cells were first cultured for 96 hours In serum-free medium containing Flt3 ligand, Steel factor, interieukin-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-beta(1) for 48 hours. Exposure to SDF-1 but not TGF-beta(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. (C) 2002 by The American Society of Hematology.
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