French Blood Institute, Bordeaux, France.
INSERM U1035, University of Bordeaux, Bordeaux, France.
Leukemia. 2020 Dec;34(12):3370-3381. doi: 10.1038/s41375-020-0982-y. Epub 2020 Jul 20.
In the context of hematopoietic cell transplantation, hematopoietic stem cells and progenitor cells (HSC and HPC) are usually collected by apheresis following their mobilization by G-CSF alone or in combination with Plerixafor® when patients fail to respond to G-CSF alone. In medical practice, the quality of the hematopoietic graft is based on CD34 cell content that is used to define "Good Mobilizer (GM)" or "Poor Mobilizer (PM)" patients but does not report the real HSC content of grafts. In this study, we assessed the HSC content within the CD34 fraction of graft samples from 3 groups of patients: 1-GM patients receiving G-CSF only (GM), 2-PM patients receiving G-CSF only (PM), 3-PM patients receiving G-CSF + Plerixafor (PM). Although HSC from the 3 groups of patients displayed very similar phenotypic profiles, expression of "stemness" genes and metabolic characteristics, their capacity to engraft NSG mice differed revealing differences in terms of HSC between groups. Indeed according to mobilization regimen, we observed differences in migration capacity of HSC, as well as differences in engraftment intensity depending on the initial pathology (myeloma versus lymphoma) of patients. This suggests that mobilization regimen could strongly influence the long term engraftment efficiency of hematopoietic grafts.
在造血细胞移植的背景下，造血干细胞和祖细胞（HSC 和 HPC）通常通过单独使用 G-CSF 或在 G-CSF 联合 Plerixafor®动员后通过单采来收集，当患者对单独使用 G-CSF 无反应时。在医疗实践中，造血移植物的质量基于 CD34 细胞含量，用于定义“良好动员者（GM）”或“不良动员者（PM）”患者，但不报告移植物的真实 HSC 含量。在这项研究中，我们评估了来自 3 组患者的移植物样本中 CD34 部分的 HSC 含量：1-仅接受 G-CSF 的 GM 患者（GM），2-仅接受 G-CSF 的 PM 患者（PM），3-接受 G-CSF+Plerixafor 的 PM 患者（PM）。尽管来自 3 组患者的 HSC 显示出非常相似的表型特征、“干性”基因表达和代谢特征，但它们在 NSG 小鼠中的植入能力不同，表明组间 HSC 存在差异。事实上，根据动员方案，我们观察到 HSC 迁移能力的差异，以及根据患者的初始病理（骨髓瘤与淋巴瘤）的植入强度的差异。这表明动员方案可能会强烈影响造血移植物的长期植入效率。
