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Mobilizing stem cells from normal donors: is it possible to improve upon G-CSF?

机译:动员正常供体的干细胞:是否可以改善G-CSF?

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Currently, granulocyte colony stimulating factor (G-CSF) remains the standard mobilizing agent for peripheral blood stem cell (PBSC) donors, allowing the safe collection of adequate PBSCs from the vast majority of donors. However, G-CSF mobilization can be associated with some significant side effects and requires a multi-day dosing regimen. The other cytokine approved for stem cell mobilization, granulocyte-macrophage colony stimulating factor (GM-CSF), alters graft composition and may reduce the development of graft-versus-host disease, but a significant minority of donors fails to provide sufficient CD34+ cells with GM-CSF and some experience unacceptable toxicity. AMD3100 is a promising new mobilizing agent, which may have several advantages over G-CSF for donor mobilization. As it is a direct antagonist of the interaction between the chemokine stromal-derived factor-1 and its receptor CXCR4, AMD3100 mobilizes PBSCs within hours rather than days. It is also well tolerated, with no significant side effects reported in any of the clinical trials to date. Studies of autologous and allogeneic transplantation of AMD3100 mobilized grafts have demonstrated prompt and stable engraftment. Here, we review the current state of stem cell mobilization in normal donors and discuss novel strategies for donor stem cell mobilization.
机译:目前,粒细胞集落刺激因子(G-CSF)仍然是外周血干细胞(PBSC)供体的标准动员剂,可以安全地从绝大多数供体中收集足够的PBSC。但是,动员G-CSF可能会带来一些明显的副作用,并且需要多日的给药方案。批准用于干细胞动员的另一种细胞因子粒细胞-巨噬细胞集落刺激因子(GM-CSF),可改变移植物组成并可能减少移植物抗宿主病的发生,但相当一部分的供体未能提供足够的CD34 +细胞。 GM-CSF和某些药物具有不可接受的毒性。 AMD3100是一种有前途的新型动员剂,在供体动员方面可能比G-CSF具有多个优势。由于它是趋化因子基质衍生因子-1与其受体CXCR4之间相互作用的直接拮抗剂,因此AMD3100可在数小时而不是数天内动员PBSC。它也具有良好的耐受性,迄今为止在任何临床试验中均未报告明显的副作用。 AMD3100动员移植物的自体和同种异体移植研究表明,移植能够迅速,稳定地进行。在这里,我们回顾了正常供体中干细胞动员的当前状态,并讨论了供体干细胞动员的新策略。

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