Optimizing stem cell infusion timing in the prevention of acute graft-versus-host disease

IF 45.5 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Cell Pub Date : 2025-03-31 DOI:10.1016/j.cell.2025.03.022
Yiwen Hou, Yue Wu, Yang Cao, Xiaoxia Hu, Yuqian Sun, Hongmei Wang, Liang Wang, Jialin Zhou, Zhonglin Zhang, Zhiwei Liu, Baolin Tang, Kaidi Song, Guangyu Sun, Wen Gao, Tianqi Zheng, Ping Wu, Weiwei Wu, Dapeng Ju, Xiaoyu Zhu, Cheng Zhan
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引用次数: 0

Abstract

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a cornerstone treatment for a broad spectrum of malignant and nonmalignant hematological disorders. However, the success of allo-HSCT is often overshadowed by acute graft-versus-host disease (aGVHD), a life-threatening complication. Here, we show in patients and murine models that the circadian timing of stem cell infusion dictates the development of aGVHD. Early-infused patients exhibit a significantly lower incidence and severity of aGVHD, as well as improved survival. We observed time-of-day variations in the levels of cytokines, especially IL-1α, which controls donor T cell responses after transplantation. The levels of IL-1α in patients were strongly associated with the development of aGVHD. Furthermore, preclinical results showed that the administration of IL-1α neutralizing antibodies markedly alleviated aGVHD and increased survival. Our study suggests that scheduling stem cell infusions early in the day could be a simple yet transformative intervention for preventing aGVHD.

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来源期刊
Cell
Cell 生物-生化与分子生物学
CiteScore
110.00
自引率
0.80%
发文量
396
审稿时长
2 months
期刊介绍: Cells is an international, peer-reviewed, open access journal that focuses on cell biology, molecular biology, and biophysics. It is affiliated with several societies, including the Spanish Society for Biochemistry and Molecular Biology (SEBBM), Nordic Autophagy Society (NAS), Spanish Society of Hematology and Hemotherapy (SEHH), and Society for Regenerative Medicine (Russian Federation) (RPO). The journal publishes research findings of significant importance in various areas of experimental biology, such as cell biology, molecular biology, neuroscience, immunology, virology, microbiology, cancer, human genetics, systems biology, signaling, and disease mechanisms and therapeutics. The primary criterion for considering papers is whether the results contribute to significant conceptual advances or raise thought-provoking questions and hypotheses related to interesting and important biological inquiries. In addition to primary research articles presented in four formats, Cells also features review and opinion articles in its "leading edge" section, discussing recent research advancements and topics of interest to its wide readership.
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