Sikorová Miriama, Klener Pavel, Tonarová Pavla, Kalbáčová Marie Hubálek
Institute of Pathological Physiology, 1st Faculty of Faculty of Medicine, Charles University, U nemocnice 5, Prague, 128 53, Czech Republic.
BMC Cancer. 2025 Apr 14;25(1):678. doi: 10.1186/s12885-025-13988-2.
Leukemia is driven by complex interactions within the inherently hypoxic bone marrow microenvironment, impacting both disease progression and therapeutic resistance. Co-cultivation of leukemic cells with feeder cells has emerged as a valuable tool to mimic the bone marrow niche. This study explores the interplay between human commercial SD-1 and patient-derived UPF26K leukemic cell lines with feeders - human fibroblasts (NHDF) and mesenchymal stem cells (hMSCs) under normoxic and hypoxic conditions.
Co-cultivation with feeders significantly enhances proliferation and glycolytic activity in the SD-1 cells, improving their viability, while this interaction inhibits the growth and glucose metabolism of the feeders, particularly NHDF. In contrast, UPF26K cells show reduced proliferation when co-cultivated with the feeders while this interaction stimulates NHDF and hMSCs proliferation and glycolysis but reduce their mitochondrial metabolism with hypoxia amplifying these effects.
Cells that switch to glycolysis during co-cultivation, particularly under hypoxia, benefit most from these low oxygen conditions. Due to this leukemic cells' response heterogeneity, targeting microenvironmental interactions and oxygen levels is crucial for personalized leukemia therapy. Advancing co-cultivation models, particularly through innovations like spheroids, can further enhance in vitro studies of primary leukemic cells and support the testing of novel therapies.
白血病是由本质上缺氧的骨髓微环境中的复杂相互作用驱动的，这会影响疾病进展和治疗抗性。白血病细胞与饲养细胞共培养已成为模拟骨髓生态位的一种有价值的工具。本研究探讨了在常氧和缺氧条件下，人商用SD-1细胞系和患者来源的UPF26K白血病细胞系与饲养细胞——人成纤维细胞（NHDF）和间充质干细胞（hMSCs）之间的相互作用。
与饲养细胞共培养显著增强了SD-1细胞的增殖和糖酵解活性，提高了它们的活力，而这种相互作用抑制了饲养细胞，特别是NHDF的生长和葡萄糖代谢。相比之下，UPF26K细胞与饲养细胞共培养时增殖减少，而这种相互作用刺激了NHDF和hMSCs的增殖及糖酵解，但降低了它们的线粒体代谢，缺氧会放大这些影响。
在共培养过程中转向糖酵解的细胞，尤其是在缺氧条件下，从这些低氧条件中获益最大。由于这种白血病细胞的反应异质性，针对微环境相互作用和氧水平进行靶向治疗对于个性化白血病治疗至关重要。推进共培养模型，特别是通过类球体等创新方法，可以进一步加强对原发性白血病细胞的体外研究，并支持新型疗法的测试。
