Department of Hematology, Second Affiliated Hospital of Soochow University, Suzhou, P.R. China.
Arch Med Res. 2010 Nov;41(8):623-33. doi: 10.1016/j.arcmed.2010.11.008.
Abnormality of immune regulation exists in multiple myeloma (MM). Mesenchymal stem cells (MSCs), a key regulator for immunomodulatory function, have decreased osteogenic potential in MM patients. Here we investigated the immunomodulatory function of MSCs from MM patients (MM-MSCs) and its relationship with decreased osteogenic potential.
Real-time PCR was performed to detect the cytokines expressed in MM-MSCs (n = 22) and MSCs from normal donors (ND-MSCs, n = 11). Lymphocyte proliferative assay was used to detect the effect of MSCs on T cell proliferation. The effect of MSCs on T-cell cycle and T-cell activation markers expression were analyzed by flow cytometry. Flow cytometry and Western blot were used to detect apoptosis of T cells. Influence of T cells on osteogenic potential of MSCs was detected.
MM-MSCs exhibited increased expression of TGF-β1, IL-6, IL-3, TNF-α and RANKL and decreased expression of TGF-β2, TGF-β3 and FasL. The inhibitory effect of MM-MSCs on T.cell proliferative ability was attenuated. ND-MSCs silence more T cells in G0/G1 phase than MM-MSCs. The apoptosis-promoting effect of MM-MSCs on T cells seemed to be dampened. Expression of T-cell activation markers was significantly inhibited by ND-MSCs. T cells from normal donors possessed the ability to promote osteoblastic differentiation of ND-MSCs, but this ability of T cells both directly from MM patients and co-cultured with MM-MSCs was impaired.
MSCs from MM patients showed impaired immunoinhibitory capability on T cells, which in turn lose the ability to stimulate osteogenesis of MSCs.
多发性骨髓瘤（MM）存在免疫调节异常。间充质干细胞（MSCs）是免疫调节功能的关键调节因子，在 MM 患者中其成骨潜能降低。在此，我们研究了 MM 患者来源的间充质干细胞（MM-MSCs）的免疫调节功能及其与成骨潜能降低的关系。
采用实时 PCR 检测 MM-MSCs（n=22）和正常供体来源的间充质干细胞（ND-MSCs，n=11）中细胞因子的表达。采用淋巴细胞增殖试验检测 MSCs 对 T 细胞增殖的影响。采用流式细胞术分析 MSCs 对 T 细胞周期和 T 细胞活化标志物表达的影响。采用流式细胞术和 Western blot 检测 T 细胞凋亡。检测 T 细胞对 MSCs 成骨潜能的影响。
MM-MSCs 表现出 TGF-β1、IL-6、IL-3、TNF-α和 RANKL 表达增加，而 TGF-β2、TGF-β3 和 FasL 表达减少。MM-MSCs 抑制 T 细胞增殖能力的作用减弱。ND-MSCs 将更多的 T 细胞阻滞在 G0/G1 期，而 MM-MSCs 则较少。MM-MSCs 促进 T 细胞凋亡的作用似乎减弱。ND-MSCs 显著抑制 T 细胞活化标志物的表达。来自正常供体的 T 细胞具有促进 ND-MSCs 成骨分化的能力，但 T 细胞直接来自 MM 患者或与 MM-MSCs 共培养时，这种能力受损。
MM 患者的 MSCs 对 T 细胞的免疫抑制能力受损，进而丧失刺激 MSCs 成骨的能力。
