Kemna Koen, van der Burg Mirjam, Lankester Arjan, Giera Martin
Department of Pediatrics, Laboratory for Pediatric Immunology, Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, The Netherlands.
Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands.
Bioessays. 2025 Feb;47(2):e2400154. doi: 10.1002/bies.202400154. Epub 2024 Nov 6.
Hematopoiesis unfolds within the bone marrow niche where hematopoietic stem cells (HSCs) play a central role in continually replenishing blood cells. The hypoxic bone marrow environment imparts peculiar metabolic characteristics to hematopoietic processes. Here, we discuss the internal metabolism of HSCs and describe external influences exerted on HSC metabolism by the bone marrow niche environment. Importantly, we suggest that the metabolic environment and metabolic cues are intertwined with HSC cell fate, and are crucial for hematopoietic processes. Metabolic dysregulation within the bone marrow niche during acute stress, inflammation, and chronic inflammatory conditions can lead to reduced HSC vitality. Additionally, we raise questions regarding metabolic stresses imposed on HSCs during implementation of stem cell protocols such as allo-SCT and gene therapy, and the potential ramifications. Enhancing our comprehension of metabolic influences on HSCs will expand our understanding of pathophysiology in the bone marrow and improve the application of stem cell therapies.
造血过程在骨髓微环境中展开,造血干细胞(HSCs)在持续补充血细胞方面发挥着核心作用。缺氧的骨髓环境赋予造血过程独特的代谢特征。在此,我们讨论造血干细胞的内部代谢,并描述骨髓微环境对造血干细胞代谢产生的外部影响。重要的是,我们认为代谢环境和代谢信号与造血干细胞的细胞命运相互交织,对造血过程至关重要。在急性应激、炎症和慢性炎症状态下,骨髓微环境内的代谢失调会导致造血干细胞活力下降。此外,我们还提出了有关在异基因造血干细胞移植(allo-SCT)和基因治疗等干细胞方案实施过程中施加于造血干细胞的代谢应激及其潜在后果的问题。加强我们对代谢对造血干细胞影响的理解将扩展我们对骨髓病理生理学的认识,并改善干细胞疗法的应用。