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免疫调节可溶性介质的健康供者谱受干细胞动员和单采的影响而改变。

The healthy donor profile of immunoregulatory soluble mediators is altered by stem cell mobilization and apheresis.

机构信息

Department of Immunology and Transfusion Medicine, Haukeland University Hospital, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway.

Department of Biomedical Laboratory Sciences and Chemical Engineering, Faculty of Engineering and Business Administration, Bergen University College, Bergen, Norway.

出版信息

Cytotherapy. 2018 May;20(5):740-754. doi: 10.1016/j.jcyt.2018.02.366. Epub 2018 Mar 22.

DOI:10.1016/j.jcyt.2018.02.366
PMID:29576502
Abstract

BACKGROUND

Peripheral blood stem cells from healthy donors mobilized by granulocyte colony-stimulating factor (G-CSF) and thereafter harvested by leukapheresis are commonly used for allogeneic stem cell transplantation.

METHODS

Plasma levels of 38 soluble mediators (cytokines, soluble adhesion molecules, proteases, protease inhibitors) were analyzed in samples derived from healthy stem cell donors before G-CSF treatment and after 4 days, both immediately before and after leukapheresis.

RESULTS

Donors could be classified into two main subsets based on their plasma mediator profile before G-CSF treatment. Seventeen of 36 detectable mediators were significantly altered by G-CSF; generally an increase in mediator levels was seen, including pro-inflammatory cytokines, soluble adhesion molecules and proteases. Several leukocyte- and platelet-released mediators were increased during apheresis. Both plasma and graft mediator profiles were thus altered and showed correlations to graft concentrations of leukocytes and platelets; these concentrations were influenced by the apheresis device used. Finally, the mediator profile of the allotransplant recipients was altered by graft infusion, and based on their day +1 post-transplantation plasma profile our recipients could be divided into two major subsets that differed in overall survival.

DISCUSSION

G-CSF alters the short-term plasma mediator profile of healthy stem cell donors. These effects together with the leukocyte and platelet levels in the graft determine the mediator profile of the stem cell grafts. Graft infusion also alters the systemic mediator profile of the recipients, but further studies are required to clarify whether such graft-induced alterations have a prognostic impact.

摘要

背景

健康供者经粒细胞集落刺激因子(G-CSF)动员后产生的外周血造血干细胞,然后通过白细胞分离术采集,常用于异基因造血干细胞移植。

方法

在 G-CSF 治疗前和治疗后 4 天,即白细胞分离术前后,分别分析来自健康干细胞供者的样本中 38 种可溶性介质(细胞因子、可溶性黏附分子、蛋白酶、蛋白酶抑制剂)的血浆水平。

结果

根据 G-CSF 治疗前的血浆介质谱,可将 36 种可检测介质中的 17 种分为两个主要亚群。G-CSF 显著改变了 17 种可检测介质;一般来说,介质水平升高,包括促炎细胞因子、可溶性黏附分子和蛋白酶。在白细胞分离术中,几种白细胞和血小板释放的介质增加。因此,血浆和移植物介质谱都发生了改变,并与白细胞和血小板的移植物浓度相关;这些浓度受所用白细胞分离设备的影响。最后,移植物输注改变了同种异体移植受者的介质谱,基于移植后第 1 天的血浆谱,我们的受者可以分为两个主要亚群,它们在总体存活率上存在差异。

讨论

G-CSF 改变了健康干细胞供者的短期血浆介质谱。这些影响以及移植物中的白细胞和血小板水平决定了干细胞移植物的介质谱。移植物输注也改变了受者的全身介质谱,但需要进一步研究来阐明这种移植物诱导的改变是否具有预后意义。

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