Glucose oxidase induces mobilization of long-term repopulating hematopoietic cells in mice,STEM CELLS Translational Medicine

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Glucose oxidase induces mobilization of long-term repopulating hematopoietic cells in mice
STEM CELLS Translational Medicine ( IF 5.4 ) Pub Date : 2021-06-23 , DOI: 10.1002/sctm.20-0514
Han-Sol So ₁ , Min-Guk Kim _{1,

2} , Jeong-Chae Lee _{1,

2} , Sung-Ho Kook ₁

Affiliation

Hematopoietic stem progenitor cells (HSPCs) mobilized to peripheral blood, rather than those remaining in the bone marrow (BM), are commonly used as stem cell source in the clinic. As reactive oxygen species (ROS) are suggested as mediator of HSPC mobilization, we examined the impacts of glucose oxidase (GO) on peripheral mobilization of BM HSPCs and the associated mechanisms. Intravenous injection of GO induced HSPC mobilization even by single treatment, and the GO-mobilized cells maintained their long-term reconstituting and differentiating potentials in conditioned recipients. GO-injected mice lived a normal life without adverse effects such as stem cell senescence, hematopoietic disorders, and blood parameter alteration. The mobilization effect of GO was even evident in animal models showing poor mobilization, such as old, 5-fluorouracil-treated, or alendronate-treated mice. Importantly, combined injection of GO with granulocyte colony-stimulating factor (G-CSF) and/or AMD3100 enhanced more greatly HSPC mobilization than did G-CSF, AMD3100, or both. The GO-stimulated HSPC mobilization was almost completely attenuated by N-acetyl-L-cysteine treatment. Collectively, our results not only highlight the potential role of GO in HSPC mobilization via ROS signaling, but also provide a GO-based new strategy to improve HSPC mobilization in poorly mobilizing allogeneic or autologous donors via combination with G-CSF and/or AMD3100.

中文翻译：

葡萄糖氧化酶诱导小鼠长期再生造血细胞的动员

造血干祖细胞 (HSPC) 动员到外周血，而不是留在骨髓 (BM) 中的那些，通常用作临床中的干细胞来源。由于活性氧 (ROS) 被认为是 HSPC 动员的介质，我们研究了葡萄糖氧化酶 (GO) 对 BM HSPC 外周动员的影响及其相关机制。即使通过单次处理，静脉内注射 GO 也能诱导 HSPC 动员，并且 GO 动员的细胞在条件受体中保持其长期重组和分化潜能。注射 GO 的小鼠过着正常的生活，没有干细胞衰老、造血障碍和血液参数改变等副作用。GO 的动员效果甚至在动员较差的动物模型中也很明显，例如年老、5-氟尿嘧啶处理或阿仑膦酸盐处理的小鼠。重要的是，GO 与粒细胞集落刺激因子 (G-CSF) 和/或 AMD3100 的联合注射比 G-CSF、AMD3100 或两者更能增强 HSPC 的动员。GO 刺激的 HSPC 动员几乎完全减弱N-乙酰-L-半胱氨酸处理。总的来说，我们的研究结果不仅突出了 GO 通过 ROS 信号传导在 HSPC 动员中的潜在作用，而且还提供了一种基于 GO 的新策略，通过与 G-CSF 和/或 AMD3100 的组合来改善 HSPC 动员在动员不良的同种异体或自体供体中的作用。

更新日期：2021-06-23

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