中国科技大学占成团队发现,提高干细胞滴注时间,防止急性移植物抗宿主病。2025年3月31日,世界著名学术期刊《细胞》发布了这一成果。
研究小组成员在患者和老鼠模型中解释说,干细胞炎症的昼夜节律决定了AGVHD的发展。早期炎症患者的AGVHD患病率和严重程度明显降低,存活率也有所提高。研究小组观察细胞因子水平的时间变化,特别是IL-1α,对移植后的T细胞反应进行控制。病人IL-1αAGVHD的发展与水平密切相关。
另外,临床前的数据显示,IL-1α中和抗体可以显著缓解aGVHD,提高存活率。根据他们的研究,在一天的早期安排干细胞感染可能是预防aGVHD的一种简单但改变性的治疗方法。
据报道,同一异体造血干细胞移植(allo-HSCT)这是治疗恶性和非恶性血液疾病的基石。然而,急性移植物抗宿主病常成功移植同一异体造血干细胞。(aGVHD)(一种危及生命的疾病)所掩盖。
附:英文原文
Title: Optimizing stem cell infusion timing in the prevention of acute graft-versus-host disease
Author: 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
Issue&Volume: 2025-03-31
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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