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骨髓脂肪组织:成骨细胞龛、造血和血液系统恶性肿瘤的调控。

Bone Marrow Adipose Tissue: Regulation of Osteoblastic Niche, Hematopoiesis and Hematological Malignancies.

机构信息

Department of Physiology and Cellular Biophysics, Columbia University, New York, NY, USA.

Institute for Orthopedy Banjica, Belgrade, Serbia.

出版信息

Stem Cell Rev Rep. 2023 Jul;19(5):1135-1151. doi: 10.1007/s12015-023-10531-3. Epub 2023 Mar 17.

Abstract

Bone marrow adipose tissue (BMAT) creates a specific microniche within multifunctional bone marrow (BM) ecosystem which imposes changes in surrounding cells and at systemic level. Moreover, BMAT contributes to spatial and temporal separation and metabolic compartmentalization of BM, thus regulating BM homeostasis and diseases. Recent findings have identified novel progenitor subsets of bone marrow adipocytes (BMAd)s recruited during the BM adipogenesis within different skeletal and hematopoietic stem cell niches. Potential of certain mesenchymal BM cells to differentiate into both osteogenic and adipogenic lineages, contributes to the complex interplay of BMAT with endosteal (osteoblastic) niche compartments as an important cellular player in bone tissue homeostasis. Targeting and ablation of BMAT cells at certain states might be an optional and promising strategy for improvement of bone health. Additionally, recent findings demonstrated spatial distribution of BMAds related to hematopoietic cells and pointed out important functional roles in the vital processes such as long-term hematopoiesis. BM adipogenesis appears to be an emergency phenomenon that follows the production of hematopoietic stem and progenitor cell niche factors, thus regulating physiological, stressed, and malignant hematopoiesis. Lipolytic and secretory activity of BMAds can influence survival and proliferation of hematopoietic cells at different maturation stages. Due to their different lipid status, constitutive and regulated BMAds are important determinants of normal and malignant hematopoietic cells. Further elucidation of cellular and molecular players involved in BMAT expansion and crosstalk with malignant cells is of paramount importance for conceiving the new therapies for improvement of BM health.

摘要

骨髓脂肪组织(BMAT)在多功能骨髓(BM)生态系统内创造了一个特定的微环境,对周围细胞和全身水平都产生影响。此外,BMAT 有助于 BM 的空间和时间分离以及代谢区室化,从而调节 BM 的动态平衡和疾病。最近的研究结果确定了在不同的骨骼和造血干细胞龛中,BM 脂肪生成过程中招募的新型骨髓脂肪细胞(BMAd)前体细胞亚群。某些间充质 BM 细胞具有向成骨细胞和脂肪细胞谱系分化的潜能,这有助于 BMAT 与骨内膜(成骨细胞)龛隔间的复杂相互作用,作为骨组织动态平衡的重要细胞参与者。在某些状态下靶向和消融 BMAT 细胞可能是改善骨骼健康的一种可选且有前途的策略。此外,最近的研究结果表明,与造血细胞相关的 BMAds 的空间分布,并指出了其在长期造血等重要生命过程中的重要功能作用。BM 脂肪生成似乎是一种紧急现象,紧随造血干细胞和祖细胞龛因子的产生,从而调节生理、应激和恶性造血。BMAds 的脂肪分解和分泌活性可以影响不同成熟阶段造血细胞的存活和增殖。由于其不同的脂质状态,组成型和调节型 BMAds 是正常和恶性造血细胞的重要决定因素。进一步阐明参与 BMAT 扩张的细胞和分子参与者以及与恶性细胞的串扰对于构思改善 BM 健康的新疗法至关重要。

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