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骨髓微环境中造血干细胞及相关间充质干细胞群体的体内外模型相互作用

Interactions of Hematopoietic and Associated Mesenchymal Stem Cell Populations in the Bone Marrow Microenvironment, In Vivo and In Vitro Model.

作者信息

Bačenková Darina, Trebuňová Marianna, Dosedla Erik, Čajková Jana, Živčák Jozef

机构信息

Department of Biomedical Engineering and Measurement, Faculty of Mechanical Engineering, Technical University of Košice, Letná 9, 042 00 Košice, Slovakia.

Department of Biomedical Research and Clinical Trials, L. Pasteur University Hospital in Košice, Rastislavova 43, 041 90 Košice, Slovakia.

出版信息

Int J Mol Sci. 2025 Sep 17;26(18):9036. doi: 10.3390/ijms26189036.

Abstract

Multipotent hematopoietic stem cells (HSC) reside in specialized niches of the bone marrow (BM). The maintenance of their stemness requires a precisely regulated bone marrow microenvironment (BMM), supported by mesenchymal stem cells (MSCs), stromal reticular cells, and endothelial and nerve cells located within the vascular and endosteal niches. The heterogeneity of the niche environment is caused by the diversity of cell populations from HSCs to more mature hematopoietic cell types and MSCs, which collectively influence the complex intercellular interactions involved in hematopoiesis. MSC subclusters in BM are characterized by the phenotypes of CXC-chemokine ligand 12, leptin receptor, neuron-glial antigen 2, and Nestin+ cells. The article presents a detailed characterization of individual stem cell types in the BM, their reciprocal interaction, and the possibility of in vitro simulation of the bone marrow niche as a dynamic structure. Development of a suitable simulation of the BMM is essential for advancing research into both physiological and pathological processes of hematopoiesis. The main goal is to simulate 3D cell culture using biomaterials that mimic the BM niche in the form of hydrogels and scaffolds, in combination with extracellular matrix components.

摘要

多能造血干细胞(HSC)存在于骨髓(BM)的特定微环境中。其干性的维持需要一个由间充质干细胞(MSC)、基质网状细胞以及位于血管和骨内膜微环境中的内皮细胞和神经细胞支持的精确调控的骨髓微环境(BMM)。微环境的异质性是由从造血干细胞到更成熟造血细胞类型以及间充质干细胞的细胞群体多样性所导致的,这些细胞共同影响造血过程中复杂的细胞间相互作用。骨髓中的间充质干细胞亚群以CXC趋化因子配体12、瘦素受体、神经元胶质抗原2和巢蛋白阳性细胞的表型为特征。本文详细描述了骨髓中各个干细胞类型、它们之间的相互作用以及将骨髓微环境作为动态结构进行体外模拟的可能性。开发合适的骨髓微环境模拟对于推进造血生理和病理过程的研究至关重要。主要目标是使用以水凝胶和支架形式模拟骨髓微环境的生物材料,并结合细胞外基质成分来模拟三维细胞培养。

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