编者按：第54届国际实验血液学会年度科学会议（ISEH 2025）于9月24日至27日在日本熊本盛大召开，汇聚全球血液学领域顶尖专家，共话基础血液学、免疫学、干细胞及细胞与基因治疗等前沿进展。作为本届大会的亮点之一，中日干细胞与细胞治疗联合研讨会吸引了广泛关注。日本九州大学Fumio Arai教授在研讨会上，围绕“Signaling networks governing hematopoietic stem cell quiescence”（调控造血干细胞静息状态的信号网络）主题进行了精彩分享。《肿瘤瞭望-血液时讯》特邀Fumio Arai教授就信号网络在干细胞功能维持及临床应用中的潜力进行了深入探讨。

《肿瘤瞭望-血液时讯》：在调控造血干细胞（HSC）静息状态的信号网络中，哪些关键信号通路发挥核心作用？这些通路如何维持HSC的自我更新与分化平衡？

Fumio Arai教授：造血干细胞的自我更新、静止及分化受到多条关键信号通路的精密调控。然而，由于这些信号通路并非独立运作，而是构成一个高度整合、相互作用的调控网络，因而难以孤立地评估单一通路在其中的功能权重。因此，信号通路之间的平衡尤为关键。在本次报告中，我展示了我们团队的研究成果，该发现对于维持细胞静止具有重要意义。然而，需要强调的是，其他信号通路同样不可或缺。总体而言，这些信号通路之间的相互关系对于维持造血干细胞的静止和自我更新至关重要。

Oncology Frontier-Hematology Frontier：In the signaling networks governing hematopoietic stem cell (HSC) quiescence, which key signaling pathways (such as mTOR or TGF-β pathways) play a central role? How do these pathways maintain the balance between HSC self-renewal and differentiation?
 

Prof. Fumio Arai: The self-renewal, quiescence, and differentiation of hematopoietic stem cells (HSCs) are precisely regulated by multiple key signaling pathways. However, as these pathways do not operate in isolation but form a highly integrated and interactive regulatory network, it is challenging to independently evaluate the functional contribution of any single pathway. Consequently, the balance among these signaling pathways is of paramount importance. In this presentation, I shared our team’s research findings, which underscore their significance in maintaining cellular quiescence. Nevertheless, it must be emphasized that other signaling pathways are equally essential. Overall, the interplay among these signaling pathways is critical for sustaining the quiescence and self-renewal of HSCs.

《肿瘤瞭望-血液时讯》在临床应用方面，如何利用这些信号网络知识开发新型干细胞治疗策略，例如针对骨髓衰竭或再生医学的干预？您能分享一些潜在的应用前景吗？

Fumio Arai教授：若能识别调控干细胞自我更新活性的关键信号通路，下一步的研究重点应当集中于寻找能够特异性激活这些信号的分子或方法，从而将相关发现转化为临床应用。例如，若发现某些小分子能够有效诱导干细胞自我更新所必需的关键转录因子，其潜在应用价值将非常显著，可为干细胞治疗、造血干细胞移植及相关再生医学策略提供新的干预手段。

Oncology Frontier-Hematology Frontier：In terms of clinical applications, how can knowledge of these signaling networks be leveraged to develop novel stem cell therapies, such as interventions for bone marrow failure or regenerative medicine? Can you share some potential application prospects?

Prof. Fumio Arai: If key signaling pathways regulating stem cell self-renewal activity can be identified, subsequent research should focus on discovering molecules or methods that specifically activate these pathways, thereby translating these findings into clinical applications. For example, identifying small molecules that effectively induce critical transcription factors essential for stem cell self-renewal would have significant potential, providing novel intervention strategies for stem cell therapy, hematopoietic stem cell transplantation, and related regenerative medicine approaches.

《肿瘤瞭望-血液时讯》展望未来，您认为调控HSC静息状态的信号网络研究将如何推动干细胞与细胞治疗领域的发展？是否存在哪些未解决的挑战需要进一步探索？

Fumio Arai教授：若能阐明维持细胞周期静止或保护干细胞功能的分子机制，便可利用这些知识在体外培养期间维持干细胞的功能特性。目前，体外培养造血干细胞常导致其干细胞功能的丧失，尤其是在基因编辑或基因转移过程中。若能有效保护干细胞功能并维持其自我更新活性，将对临床应用，特别是造血干细胞移植具有重要价值。然而，目前保护干细胞功能仍面临显著挑战。虽已有部分方法可用于扩增或保护造血干细胞，但仍需深入分析与优化，这些方法仍存在显著改进空间。

Oncology Frontier-Hematology Frontier：Looking to the future, how do you think research on signaling networks governing HSC quiescence will drive advancements in the field of stem cell and cell therapy? Are there any unresolved challenges that require further exploration?

Prof. Fumio Arai: If the molecular mechanisms governing the maintenance of cell cycle quiescence or the protection of stem cell function can be elucidated, this knowledge could be applied to preserve the functional properties of stem cells during in vitro culture. Currently, in vitro culture of hematopoietic stem cells frequently results in the loss of their stem cell functionality, particularly during gene editing or gene transfer processes. Effective preservation of stem cell function and maintenance of their self-renewal capacity would be of significant value for clinical applications, especially in hematopoietic stem cell transplantation. However, protecting stem cell function remains a major challenge. Although some methods exist for expanding or preserving hematopoietic stem cells, they require further in-depth analysis and optimization, with considerable room for improvement to enhance their efficacy for clinical translation.

专家简介

Fumio Arai教授

日本九州大学

医学院 干细胞生物学与医学系 教授 

医学研究生院 医疗行政与管理学系（兼任） 

医学研究生院 医学系（兼任）

医学院 医学系（兼任）