Mosteo Laura, Storer Joanna, Batta Kiran, Searle Emma J, Duarte Delfim, Wiseman Daniel H
Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, Porto, Portugal.
Epigenetics of Haematopoiesis Group, Division of Cancer Sciences, The University of Manchester, Manchester, United Kingdom.
Front Cell Dev Biol. 2021 Mar 11;9:635189. doi: 10.3389/fcell.2021.635189. eCollection 2021.
Hematopoietic stem cells interact with bone marrow niches, including highly specialized blood vessels. Recent studies have revealed the phenotypic and functional heterogeneity of bone marrow endothelial cells. This has facilitated the analysis of the vascular microenvironment in steady state and malignant hematopoiesis. In this review, we provide an overview of the bone marrow microenvironment, focusing on refined analyses of the marrow vascular compartment performed in mouse studies. We also discuss the emerging role of the vascular niche in "inflamm-aging" and clonal hematopoiesis, and how the endothelial microenvironment influences, supports and interacts with hematopoietic cells in acute myeloid leukemia and myelodysplastic syndromes, as exemplar states of malignant myelopoiesis. Finally, we provide an overview of strategies for modulating these bidirectional interactions to therapeutic effect in myeloid malignancies.
造血干细胞与骨髓生态位相互作用,包括高度特化的血管。最近的研究揭示了骨髓内皮细胞的表型和功能异质性。这有助于分析稳态和恶性造血过程中的血管微环境。在这篇综述中,我们概述了骨髓微环境,重点关注在小鼠研究中对骨髓血管区室进行的精细分析。我们还讨论了血管生态位在“炎症衰老”和克隆性造血中的新作用,以及内皮微环境在急性髓系白血病和骨髓增生异常综合征(作为恶性髓系造血的典型状态)中如何影响、支持造血细胞并与之相互作用。最后,我们概述了调节这些双向相互作用以对髓系恶性肿瘤产生治疗效果的策略。