Sorokina Tamara, Shipounova Irina, Bigildeev Alexey, Petinati Nataliya, Drize Nina, Turkina Anna, Chelysheva Ekaterina, Shukhov Oleg, Kuzmina Larisa, Parovichnikova Elena, Savchenko Valery
National Research Center for Hematology, Moscow, Russia.
Eur J Haematol. 2016 Sep;97(3):245-52. doi: 10.1111/ejh.12713. Epub 2016 Jan 3.
The development of leukemia impairs normal hematopoiesis and marrow stromal microenvironment. The aim of the investigation was to study the ability of multipotent mesenchymal stromal cells (MSCs) derived from the bone marrow of patients with leukemia to maintain normal hematopoietic progenitor cells.
MSCs were obtained from the bone marrow of 14 patients with acute lymphoblastic (ALL), 25 with myeloid (AML), and 15 with chronic myeloid (CML) leukemia. As a control, MSCs from 22 healthy donors were used. The incidence of cobblestone area forming cells (CAFC 7-8 d) in the bone marrow of healthy donor cultivated on the supportive layer of patients MSCs was measured.
The ability of MSCs from AML and ALL patients at the moment of diagnosis to maintain normal CAFC was significantly decreased when compared to donors. After chemotherapy, the restoration of ALL patients' MSCs functions was slower than that of AML. CML MSCs maintained CAFC better than donors' at the moment of diagnosis and this ability increased with treatment.
The ability of patients' MSCs to maintain normal hematopoietic progenitor cells was shown to change in comparison with MSCs from healthy donors and depended on nosology. During treatment, the functional capacity of patients' MSCs had been partially restored.
白血病的发展会损害正常造血和骨髓基质微环境。本研究的目的是探讨白血病患者骨髓来源的多能间充质基质细胞(MSC)维持正常造血祖细胞的能力。
从14例急性淋巴细胞白血病(ALL)、25例髓系白血病(AML)和15例慢性髓系白血病(CML)患者的骨髓中获取MSC。作为对照,使用了22名健康供体的MSC。测定在患者MSC支持层上培养的健康供体骨髓中鹅卵石区域形成细胞(CAFC 7 - 8天)的发生率。
与供体相比,AML和ALL患者诊断时MSC维持正常CAFC的能力显著降低。化疗后,ALL患者MSC功能的恢复比AML患者慢。CML患者的MSC在诊断时维持CAFC的能力优于供体,且这种能力随治疗而增强。
与健康供体的MSC相比,患者的MSC维持正常造血祖细胞的能力发生了变化,且取决于疾病分类。在治疗过程中,患者MSC的功能能力得到了部分恢复。