不同来源成体骨髓间充质干细胞调控免疫功能的比较研究

目的 比较霍奇金淋巴瘤(HL)、非霍奇金淋巴瘤(NHL)患者与正常人骨髓间充质干细胞(MSC)的免疫调节能力.方法 获取正常人、HL和NHL患者的骨髓MSC,用低血清培养液进行培养.采用流式细胞仪检测骨髓MSC的免疫表型;应用酶联免疫吸附试验检测骨髓MSC培养上清液中转化生长因子β1(TGF-β1)的水平;采用Transwell培养体系检测骨髓MSC抑制T淋巴细胞增殖的能力;应用混合淋巴细胞反应检测骨髓MSC抑制异体T淋巴细胞增殖的能力.结果 正常人、HL和NHL患者骨髓间充质干细胞具有相似的细胞形态和免疫表型,均具有分泌TGF-β1的能力,均不表达HLA-DR和共刺激分子CD80、CD86和CD40.HL和NHL患者骨髓MSC具有抑制异体T淋巴细胞增殖的能力,这种抑制能力随着MSC细胞数量的增加而增强,并可以被抗TGF-β1抗体所逆转.体外诱导分化后的骨髓MSC仍然具有抑制异体T淋巴细胞增殖的能力.结论 HL和NHL患者骨髓MSC具有和正常成人骨髓MSC相同的免疫调控能力,这种抑制T淋巴细胞增殖的能力不随着其体外诱导分化而改变.

Comparative study on immunomodulatory effects of mesenchymal stem cells derived from different sources

Objective To study the difference in immunomodulatory effects among non-Hodgkin lymphoma (NHL)-, Hodgkin lymphoma (HL)- and normal adult bone marrow-derived mesenthymal stem cells (MSCs). Methods MSCs were obtained from HL, NHL and normal adult bone marrow and cultured in expanded medium. Immunophenotype was investigated by FACS. The levels of cytokines were evaluated by enzyme linked immunosorbent assay (ELISA). T-cell suppression ability was evaluated by Transwell. Moreover, the immunoregulatory ability of HL-, NHL- and normal adult bone marrow-derived MSCs was detected by mixed lymphocyte culture assay. Results HL-, NHLand normal adult bone marrow-derived MSCs were similar in morphology and immunophenotype, and they did not express HLA-DR and co-stirnulatory molecules (CD40, CD80 and CD86). All HL-,NHL- and normal adult bone marrow-derived MSCs could significantly suppress T lymphocytes'proliferation in a dose-dependent manner and such an effect could be reversed by anti-TGF-β1 antibody.MSCs differentiated into various mesenchymal lineages did not alter their immunosuppressive effects on T-cell proliferation. Conclusion The similar immunomodulatory effects were found among HL-,NHL- and normal adult bone marrow-derived MSCs, which was not changed by differentiation.