Expression and function of homing-essential molecules and enhanced in vivo homing ability of human peripheral blood-derived hematopoietic progenitor cells after stimulation with stem cell factor
Expression and function of homing-essential molecules and enhanced in vivo homing ability of human peripheral blood-derived hematopoietic progenitor cells after stimulation with stem cell factor
复制标题
DOI：
10.1634/stemcells.22-4-580
复制
发表时间：
2004-01-01
期刊：
影响因子：
5.2
通讯作者：
Hennemann, B
中科院分区：
文献类型：
--
作者：
Hart, C;Drewel, D;Hennemann, B
造血干细胞（HSC）从血液到骨髓的归巢是一个多步骤的过程，包括滚动，外渗，迁移，最后粘附在正确的微环境中。本研究从临床干细胞移植后造血功能恢复的角度出发，探讨了干细胞因子（SCF）对外周血造血祖细胞α 4 β 1和α 5 β 1整合素极晚期抗原（VLA）-4和VLA-5表达及粘附功能的影响。经SCF刺激后，健康人CD 34（+）/c-kit（+）细胞VLA-4和VLA-5的表达分别从54%增加到90%和3%增加到82%。对于患者来源的细胞，增加幅度为67%至90%和12%至46%。SCF刺激后，粘附在纤连蛋白片段CH 296上的单核细胞比例从14%增加到23%。因此，功能研究显示贴壁长期培养起始细胞增加约30%。SCF刺激的HSC归巢能力的改善通过移植到亚致死剂量照射的非肥胖糖尿病scid/scid小鼠中得到证实。移植后6周，在8只接受人HSC并添加SCF的动物中，检测到深刻的多系造血移植，而在仅接受HSC的对照组中，8只动物均未移植。我们的数据提供了第一个体内证据，即细胞因子刺激可提高移植的人造血祖细胞的归巢能力。
Hematopoietic stem cell (HSC) homing from blood to bone marrow is a multistep process involving rolling, extravasation, migration, and finally adhesion in the correct microenvironment. With view to the hematopoietic recovery after clinical stem cell transplantation, we investigated the effect of stem cell factor (SCF) on the expression and the adhesive function of the alpha4beta1 and alpha5beta1 integrins very-late antigen (VLA)-4 and VLA-5 on peripheral blood-derived hematopoietic progenitor cells. After SCF stimulation, the expression of VLA-4 and VLA-5 on CD34(+)/c-kit(+) cells obtained from healthy donors increased from 54% to 90% and from 3% to 82%, respectively. For patient-derived cells, the increase was 67% to 90% and 12% to 46%. The proportion of mononuclear cells adhering to the fibronectin fragment CH296 increased by stimulation with SCF from 14% to 23%. Accordingly, functional studies showed an approximate 30% increase of adherent long-term culture-initiating cell. The improvement of the homing abilities of SCF-stimulated HSC was confirmed by transplantation into sublethally irradiated nonobese diabetic-scid/scid mice. Six weeks after the transplantation, in eight of eight animals receiving human HSC with the addition of SCF, a profound multilineage hematopoietic engraftment was detected, whereas in the control group receiving only HSC, none of eight animals engrafted. Our data provide the first in vivo evidence that stimulation with cytokines improves the homing ability of transplanted human hematopoietic progenitor cells.