Ex vivo treatment of proliferating human cord blood stem cells with stroma-derived factor-1 enhances their ability to engraft NOD/SCID mice

被引:48
作者
Glimm, H
Tang, P
Clark-Lewis, I
von Kalle, C
Eaves, C
机构
[1] British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada
[2] Univ British Columbia, Biomed Res Ctr, Vancouver, BC, Canada
[3] Univ British Columbia, Dept Biochem, Vancouver, BC, Canada
[4] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada
[5] Univ Freiburg, Dept Internal Med 1, D-7800 Freiburg, Germany
[6] Univ Freiburg, Inst Mol Med & Cell Res, D-7800 Freiburg, Germany
关键词
D O I
10.1182/blood.V99.9.3454
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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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页码:3454 / 3457
页数:4
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