Beeraka Narasimha M, Basappa Basappa, Nikolenko Vladimir N, Mahesh P A
Herman B. Wells Center for Pediatric Research, Department of Pediatrics, Indiana University School of Medicine, 1044 W. Walnut Street, R4-168, Indianapolis, IN, 46202, USA.
Department of Human Anatomy and Histology, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), 8/2 Trubetskaya Str., Moscow, 119991, Russia.
Stem Cell Rev Rep. 2025 Jan;21(1):2-27. doi: 10.1007/s12015-024-10761-z. Epub 2024 Jul 8.
Haematopoiesis within the bone marrow (BM) represents a complex and dynamic process intricately regulated by neural signaling pathways. This delicate orchestration is susceptible to disruption by factors such as aging, diabetes, and obesity, which can impair the BM niche and consequently affect haematopoiesis. Genetic mutations in Tet2, Dnmt3a, Asxl1, and Jak2 are known to give rise to clonal haematopoiesis of intermediate potential (CHIP), a condition linked to age-related haematological malignancies. Despite these insights, the exact roles of circadian rhythms, sphingosine-1-phosphate (S1P), stromal cell-derived factor-1 (SDF-1), sterile inflammation, and the complement cascade on various BM niche cells remain inadequately understood. Further research is needed to elucidate how BM niche cells contribute to these malignancies through neural regulation and their potential in the development of gene-corrected stem cells. This literature review describes the updated functional aspects of BM niche cells in haematopoiesis within the context of haematological malignancies, with a particular focus on neural signaling and the potential of radiomitigators in acute radiation syndrome. Additionally, it underscores the pressing need for technological advancements in stem cell-based therapies to alleviate the impacts of immunological stressors. Recent studies have illuminated the microheterogeneity and temporal stochasticity of niche cells within the BM during haematopoiesis, emphasizing the updated roles of neural signaling and immunosurveillance. The development of gene-corrected stem cells capable of producing blood, immune cells, and tissue-resident progeny is essential for combating age-related haematological malignancies and overcoming immunological challenges. This review aims to provide a comprehensive overview of these evolving insights and their implications for future therapeutic strategies.
骨髓内的造血过程是一个复杂而动态的过程，受到神经信号通路的精细调控。这种微妙的协调容易受到衰老、糖尿病和肥胖等因素的干扰，这些因素会损害骨髓微环境，进而影响造血功能。已知Tet2、Dnmt3a、Asxl1和Jak2基因的突变会导致具有中等潜能的克隆性造血（CHIP），这是一种与年龄相关的血液系统恶性肿瘤相关的病症。尽管有这些认识，但昼夜节律、鞘氨醇-1-磷酸（S1P）、基质细胞衍生因子-1（SDF-1）、无菌性炎症和补体级联反应对各种骨髓微环境细胞的确切作用仍未得到充分了解。需要进一步研究以阐明骨髓微环境细胞如何通过神经调节促成这些恶性肿瘤以及它们在基因校正干细胞开发中的潜力。这篇文献综述描述了在血液系统恶性肿瘤背景下骨髓微环境细胞在造血过程中的最新功能方面，特别关注神经信号传导以及放射缓解剂在急性放射综合征中的潜力。此外，它强调了基于干细胞的疗法在技术进步方面的迫切需求，以减轻免疫应激源的影响。最近的研究揭示了造血过程中骨髓内微环境细胞的微异质性和时间随机性，强调了神经信号传导和免疫监视的最新作用。能够产生血液、免疫细胞和组织驻留后代的基因校正干细胞的开发对于对抗与年龄相关的血液系统恶性肿瘤和克服免疫挑战至关重要。本综述旨在全面概述这些不断发展的见解及其对未来治疗策略的影响。
