倍他米松预处理对脐血源性造血干细胞植入的影响

IF 2.9 4区 医学 Q3 IMMUNOLOGY Archivum Immunologiae et Therapiae Experimentalis Pub Date : 2022-12-18 DOI:10.1007/s00005-022-00666-5
David Perna-Barrull, Laia Gomez-Muñoz, Silvia Rodriguez-Fernandez, Anna Gieras, Rosa M. Ampudia-Carrasco, Lidia Almenara-Fuentes, Ruth M. Risueño, Sergi Querol, Eva Tolosa, Marta Vives-Pi
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引用次数: 0

摘要

造血干细胞(HSC)移植是治疗恶性血液病的关键。脐带血(UCB)是干细胞的来源,但90%的脐带血单位由于细胞含量低而被丢弃。提高CD34+干细胞的移植能力将允许使用迄今为止被拒绝的UCB。倍他米松通过糖皮质激素受体诱导免疫细胞的长期转录组和表观基因组变化。我们推测,由于倍他米松的改善,废弃的UCB可以被利用。将UCB分离的CD34+ HSC暴露于合成糖皮质激素倍他米松和氟替卡松20 h,并在移植前测定细胞表型。在静脉转移2 - 5 × 105 CD34+ HSC前6 h对NSG小鼠进行亚致死照射(1 Gy或2 Gy)。流式细胞术观察外周血移植水平和白细胞亚群,随访20周。实验结束时,测定脾脏和骨髓中的移植物和白细胞亚群。我们证明倍他米松在恢复免疫系统稳态方面有惊人的效果。倍他米松和氟替卡松增加了CD34+造血干细胞中CXCR4的表达,降低了HLAⅱ类和CD54的表达。两种糖皮质激素暴露的细胞在2只gy辐照的NSG小鼠中显示出相似的植入。有趣的是,倍他米松暴露的细胞在1只gy辐照的NSG小鼠中表现出增强的植入,与对照组相比,有增加调节性T细胞百分比的趋势。倍他米松诱导CD34+造血干细胞的改变并改善移植,导致更快的免疫系统恢复,这将有助于移植细胞的存活。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Impact of Betamethasone Pretreatment on Engrafment of Cord Blood-Derived Hematopoietic Stem Cells

Hematopoietic stem cell (HSC) transplantation is crucial to cure hematologic malignancies. Umbilical cord blood (UCB) is a source of stem cells, but 90% of UCB units are discarded due to low cellularity. Improving the engraftment capacities of CD34+ stem cells would allow the use of UCB that were so far rejected. Betamethasone induces long-term transcriptomic and epigenomic changes in immune cells through glucocorticoid receptor. We hypothesize that discarded UCB could be used owing to improvements induced by betamethasone. Isolated CD34+ HSC from UCB were exposed to the synthetic glucocorticoids betamethasone and fluticasone for 20 h, and cell phenotype was determined before transplantation. NSG mice were sub-lethally irradiated (1 Gy or 2 Gy) 6 h before intravenously transferring 2–5 × 105 CD34+ HSC. The peripheral blood engraftment levels and the leukocyte subsets were followed up for 20 weeks using flow cytometry. At end point, the engraftment and leukocyte subsets were determined in the spleen and bone marrow. We demonstrated that betamethasone has surprising effects in recovering immune system homeostasis. Betamethasone and fluticasone increase CXCR4 and decrease HLA class II and CD54 expression in CD34+ HSCs. Both glucocorticoids-exposed cells showed a similar engraftment in 2 Gy-irradiated NSG mice. Interestingly, betamethasone-exposed cells showed enhanced engraftment in 1 Gy-irradiated NSG mice, with a trend to increase regulatory T cell percentage when compared to control. Betamethasone induces alterations in CD34+ HSCs and improve the engraftment, leading to a faster immune system recovery, which will contribute to engrafted cells survival.

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来源期刊
CiteScore
5.90
自引率
0.00%
发文量
26
审稿时长
>12 weeks
期刊介绍: Archivum Immunologiae et Therapiae Experimentalis (AITE), founded in 1953 by Ludwik Hirszfeld, is a bimonthly, multidisciplinary journal. It publishes reviews and full original papers dealing with immunology, experimental therapy, immunogenetics, transplantation, microbiology, immunochemistry and ethics in science.
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