Department of Medicine, James P. Wilmot Cancer Institute, University of Rochester, Rochester, NY, USA.
University of Wisconsin School of Medicine and Public Health, University of Wisconsin in Madison, Madison, WI, USA.
Stem Cells. 2023 Sep 15;41(9):823-836. doi: 10.1093/stmcls/sxad050.
The study of marrow-resident mesodermal progenitors can provide important insight into their role in influencing normal and aberrant hematopoiesis as occurs in acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS). In addition, the chemokine competency of these cells provides links to the inflammatory milieu of the marrow microenvironment with additional implications for normal and malignant hematopoiesis. While in vivo studies have elucidated the structure and function of the marrow niche in murine genetic models, corollary human studies have not been feasible, and thus the use of culture-adapted mesodermal cells has provided insights into the role these rare endogenous niche cells play in physiologic, malignant, and inflammatory states. This review focuses on culture-adapted human mesenchymal stem/stromal cells (MSCs) as they have been utilized in understanding their influence in AML and MDS as well as on their chemokine-mediated responses to myeloid malignancies, injury, and inflammation. Such studies have intrinsic limitations but have provided mechanistic insights and clues regarding novel druggable targets.
骨髓间充质祖细胞的研究可以为其在影响正常和异常造血中的作用提供重要的见解，这些作用发生在急性髓细胞白血病（AML）和骨髓增生异常综合征（MDS）中。此外，这些细胞的趋化因子能力与骨髓微环境的炎症环境有关，这对正常和恶性造血有额外的影响。虽然体内研究已经阐明了鼠基因模型中骨髓龛的结构和功能，但相应的人类研究是不可行的，因此，培养适应的间充质细胞为研究这些罕见的内源性龛细胞在生理、恶性和炎症状态下所起的作用提供了深入了解。这篇综述重点介绍了作为理解其在 AML 和 MDS 中作用的工具的培养适应的人骨髓间充质干细胞（MSC），以及它们对髓性恶性肿瘤、损伤和炎症的趋化因子介导的反应。这些研究具有内在的局限性，但为新的可用药靶提供了机制上的见解和线索。
