Petinati Nataliya, Sadovskaya Aleksandra, Shipounova Irina, Dorofeeva Alena, Drize Nina, Vasilyeva Anastasia, Aleshina Olga, Pokrovskaya Olga, Kuzmina Larisa, Starchenko Sofia, Surimova Valeria, Chabaeva Yulia, Kulikov Sergey, Parovichnikova Elena
National Medical Research Center for Hematology, Moscow 125167, Russia.
Biomedicines. 2025 May 21;13(5):1265. doi: 10.3390/biomedicines13051265.
: Acute leukemia (AL) alters both hematopoiesis and the bone marrow stromal microenvironment. Attempts to develop a culture of multipotent mesenchymal stromal cells (MSCs) from AL patients' bone marrow are not always successful, as opposed to healthy donors' bone marrow. : To unveil the reason, healthy donors' MSCs were cultured in the presence of sera from healthy donors (control group) or AL patients at the onset of the disease, in short- and long-term remission, and before and after allogeneic hematopoietic stem cell transplantation (allo-HSCT). : The cell yield in the presence of patient sera was lower than in the control, regardless of the AL stage. It was assumed that the patients either lacked growth factors to sustain MSCs, or there were inhibitors of MSC growth present. The serum's ability to support MSC growth correlated with platelet count and albumin and calcium concentrations in patients' blood. Platelet-derived growth factors-PDGFA and PDGFB-are known to induce MSC growth. Their concentration in the serum of AL patients and healthy donors was analyzed. A decrease in PDGFA concentration was found in the sera of patients compared to healthy donors. PDGFB concentration was lower at disease onset, increased during remission and decreased again during relapse. PDGFB concentration correlated with platelet count, while PDGFA concentration did not. AL patients' sera reflected systemic disturbances affecting MSC growth. So far, decreases in PDGFs, albumin and calcium concentration, as well as platelet count, are the parameters that might be among the causes of this observation.
急性白血病(AL)会改变造血功能和骨髓基质微环境。与健康供体的骨髓不同,尝试从AL患者的骨髓中培养多能间充质基质细胞(MSC)并不总是成功的。为了揭示原因,将健康供体的MSC在来自健康供体(对照组)或疾病发作时、短期和长期缓解期以及异基因造血干细胞移植(allo-HSCT)前后的AL患者的血清中进行培养。无论AL处于哪个阶段,在患者血清存在的情况下细胞产量均低于对照组。推测患者要么缺乏维持MSC生长的生长因子,要么存在MSC生长抑制剂。血清支持MSC生长的能力与患者血液中的血小板计数、白蛋白和钙浓度相关。已知血小板衍生生长因子-PDGFA和PDGFB可诱导MSC生长。分析了它们在AL患者和健康供体血清中的浓度。与健康供体相比,患者血清中PDGFA浓度降低。疾病发作时PDGFB浓度较低,缓解期升高,复发期再次降低。PDGFB浓度与血小板计数相关,而PDGFA浓度则不然。AL患者的血清反映了影响MSC生长的全身紊乱。到目前为止,PDGFs、白蛋白和钙浓度以及血小板计数的降低可能是导致这一观察结果的原因之一。