Human progenitor cells rapidly mobilized by AMD3100 repopulate NOD/SCID mice with increased frequency in comparison to cells from the same donor mobilized by granulocyte colony stimulating factor

Human progenitor cells rapidly mobilized by AMD3100 repopulate NOD/SCID mice with increased frequency in comparison to cells from the same donor mobilized by granulocyte colony stimulating factor
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DOI:
10.1016/j.bbmt.2006.12.445
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发表时间:
2007-04-01
影响因子:
4.3
通讯作者:
Nolta, Jan A.
Nolta, Jan A.
中科院分区:
医学2区
文献类型:
--
作者:
Hess, David A.;Bonde, Jesper;Nolta, Jan A.

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AMD 3100抑制SDF-1和CXCR 4之间的相互作用,并快速动员造血祖细胞用于临床移植。然而,在同一供体中,与粒细胞集落刺激因子(G-CSF)动员的细胞相比,用AMD 3100动员的人细胞的重建功能尚未得到表征。因此,在注射AMD 3100后4小时对健康供体进行白细胞分离;药物清除10天后,用G-CSF动员同一供体,允许通过动员细胞进行再增殖的配对比较。将单个核细胞(MNC)或纯化的CD 34(+)细胞以有限稀释法移植到NOD/SCID小鼠中进行比较。与来自配对供体的G-CSF动员的MNC相比,人AMD 3100动员的MNC具有增强的再填充频率,并且纯化的CD 34(+)祖细胞至少与G-CSF动员的细胞一样有效。NOD/SCID再生细胞(SRQC)的频率为8.7 × 10(6)个AMD 3100动员的MNC中1个SRC,而29.0 × 10(6)个G-CSF动员的MNC中1个SRC,1.2 × 10(5)个AMD 3100动员的CD 34(+)细胞中1个SRC,而1.8 × 10(5)个G-CSF动员的CD 34(+)细胞中1个SRC。移植祖细胞的造血分化在AMD 3100或G-CSF动员后相似。因此,AMD 3100动员的外周血代表了用于临床移植的快速获得的、高度再生的造血祖细胞来源。(c)2007年美国血液和骨髓移植学会。
AMD3100 inhibits the interaction between SDF-1 and CXCR4, and rapidly mobilizes hematopoietic progenitors for clinical transplantation. However, the repopulating function of human cells mobilized with AMD3100 has not been characterized in comparison to cells mobilized with granulocyte-colony stimulating factor (G-CSF) in the same donor. Therefore, healthy donors were leukapheresed 4 hours after injection with AMD3100; after 10 days of drug clearance the same donor was mobilized with G-CSF, allowing a paired comparison of repopulation by mobilized cells. Transplantation of mononuclear cells (MNC) or purified CD34(+) cells was compared at limiting dilution into NOD/SCID mice. Human AMD3100-mobilized MNC possessed enhanced repopulating frequency in comparison to G-CSF-mobilized MNC from paired donors, and purified CD34(+) progenitors were at least as efficient as the G-CSF mobilized cells. The frequencies of NOD/SCID repopulating cells (SRQC) were 1 SRC in 8.7 X 10(6) AMD3100-mobilized MNC compared to I SRC in 29.0 X 10(6) G-CSF-mobilized MNC, and 1 SRC in 1.2 X 10(5) AMD3100-mobilized CD34(+) cells compared to 1 SRC in 1.8 x 10(5) G-CSF-mobilized CD34(+) cells. Hematopoietic differentiation of transplanted progenitors was similar after AMD3100 or G-CSF-mobilization. Thus, AMD3100 mobilized peripheral blood represents a rapidly obtained, highly repopulating source of hematopoietic progenitors for clinical transplantation. (c) 2007 American Society for Blood and Marrow Transplantation.