Rapid and efficient homing of human CD34+CD38-/lowCXCR4+ stem and progenitor cells to the bone marrow and spleen of NOD/SCID and NOD/SCID/B2mnull mice
Rapid and efficient homing of human CD34+CD38-/lowCXCR4+ stem and progenitor cells to the bone marrow and spleen of NOD/SCID and NOD/SCID/B2mnull mice
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DOI：
10.1182/blood.v97.10.3283
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发表时间：
2001-05-15
期刊：
影响因子：
20.3
通讯作者：
Lapidot, T
中科院分区：
文献类型：
--
作者：
Kollet, O;Spiegel, A;Lapidot, T
干细胞归巢到骨微环境中是骨髓源性血细胞启动的第一步。据报道，人严重联合免疫缺陷（SCID）细胞的家，并迅速积累，在几个小时内，在骨髓和脾脏的免疫缺陷小鼠预先与全身照射条件。能够移植原代和二代受体小鼠的原始CD 34（+）CD 38（-/低）CXCR 4（+）细胞选择性地归巢至骨髓和脾脏，而未检测到CD 34（-）CD 38（-/低）Lin（-）细胞。此外，尽管新鲜分离的CD 34（+）CD 38（+/high）细胞不能归巢，但作为动员过程一部分的粒细胞集落刺激因子体内刺激或体外干细胞因子刺激2 - 4天，可增强姜黄素刺激的CD 34（+）CD 38（+）细胞的归巢能力。富集的人CD 34（+）细胞的归巢可通过抗CXCR 4抗体预处理抑制。此外，原始的CD 34（+）CD 38（-/低）CXCR 4（+）细胞也对梯度的人基质细胞衍生因子1（SDF-1）有归巢反应，直接注射到未照射的NOD/SCID小鼠的骨髓或脾脏中。用主要整合素VLA-4、VLA-5和LFA-1的抗体预处理CD 34（+）细胞也可抑制归巢。百日咳毒素是G α（i）蛋白介导的信号抑制剂，可抑制SDF-1介导的体外transwell迁移，但不抑制粘附或体内CD 34（+）细胞归巢。人CD 34（+）细胞的归巢也被一种广谱蛋白激酶C抑制剂chelerythrine chloride阻断。这项研究揭示了原始人CD 34（+）CD 38（-/低）CXCR 4（+）细胞快速有效地归巢到小鼠骨髓，该细胞是整合素介导的，并依赖于SDF-1激活蛋白激酶C信号转导途径。（血。2001;97：3283-3291）（C）2001由美国血液学学会。
Stem cell homing into the bone microenvironment is the first step in the initiation of marrow-derived blood cells. It is reported that human severe combined immunodeficient (SCID) repopulating cells home and accumulate rapidly, within a few hours, in the bone marrow and spleen of immunodeficient mice previously conditioned with total body irradiation. Primitive CD34(+)CD38(-/low)CXCR4(+) cells capable of engrafting primary and secondary recipient mice selectively homed to the bone marrow and spleen, whereas CD34(-)CD38(-/low)Lin(-) cells were not detected. Moreover, whereas freshly isolated CD34(+)CD38(+/high) cells did not home, in vivo stimulation with granulocyte colony-stimulating factor as part of the mobilization process, or in vitro stem cell factor stimulation for 2 to 4 days, potentiated the homing capabilities of cytokine-stimulated CD34(+)CD38(+) cells. Homing of enriched human CD34(+) cells was inhibited by pretreatment with anti-CXCR4 antibodies. Moreover, primitive CD34(+)CD38(-/low)CXCR4(+) cells also homed in response to a gradient of human stromal cell-derived factor 1 (SDF-1), directly injected into the bone marrow or spleen of nonirradiated NOD/SCID mice. Homing was also inhibited by pretreatment of CD34(+) cells with antibodies for the major integrins VLA-4, VLA-5, and LFA-1. Pertussis toxin, an inhibitor of signals mediated by G alpha (i) proteins, inhibited SDF-1-mediated in vitro transwell migration but not adhesion or in vivo homing of CD34(+) cells. Homing of human CD34(+) cells was also blocked by chelerythrine chloride, a broad-range protein kinase C inhibitor. This study reveals rapid and efficient homing to the murine bone marrow by primitive human CD34(+)CD38(-/low)CXCR4(+) cells that is integrin mediated and depends on activation of the protein kinase C signal transduction pathway by SDF-1. (Blood. 2001;97: 3283-3291) (C) 2001 by The American Society of Hematology.