多发性骨髓瘤间充质干细胞对树突状细胞功能的影响

Immunoregulation of mesenchymal stem cells on dendritic cells in multiple myeloma

目的探讨多发性骨髓瘤(MM)患者骨髓来源的间充质干细胞(MSC)对树突状细胞(DC)分化、成熟和细胞因子分泌及其对DC辅助T细胞杀伤骨髓瘤细胞作用的影响。方法将从MM患者骨髓来源的MSC、正常供者外周血来源的DC及骨髓瘤细胞系U266细胞进行混合培养。流式细胞术测定DC的免疫表型,ELISA法测定上清液IL-12的含量,AnnexinV-FITC/PI双标记流式细胞术测定骨髓瘤细胞凋亡比例。结果MSC能抑制rhTNF-α诱导的不成熟和成熟DC的CD1a、CD11c、CD80、CD86和HLA-DR表达(P<0.01),并显著减少成熟DC分泌IL-12(P<0.01)。MSC可以下调成熟DC的CD83表达,使其趋于不成熟状态(P<0.01)。与未加入MSC组相比,MSC混合培养组凋亡骨髓瘤细胞明显减少(P<0.01);比较MM患者与正常供者骨髓来源的MSC对DC辅助T细胞诱导骨髓瘤细胞凋亡的影响,前者U266细胞凋亡比例比后者明显减少(P<0.01)。结论MM患者骨髓来源的MSC可以抑制DC的分化、成熟和分泌细胞因子;无论是MM患者或正常供者骨髓来源MSC均可以抑制DC辅助T细胞对骨髓瘤细胞的凋亡诱导作用,且MM患者来源的MSC的作用更强。

Objective To investigate the effects of mesenchymal stem cells （MSCs） derived from multiple myeloma patients on monocyte-derived dendritic cells（DCs） ,and to compare anti-myeloma response of DCs affect by MSCs derived from multiple myeloma patients （MM-MSCs） and normal donors （ND- MSCs）. Methods MSCs derived from MM patients and healthy donors and DCs derived from healthy donor were cocultured. To study the influence of MM-MSCs on DCs differentiation and maturation, DC were cultured in the presence or absence of MSCs. To study the effect of T cell anti-myeloma response ,DCs and U266 were co-cultured with or without MSCs. Results The differentiation of DCs derived from PBMCs were significantly inhibited by MSC. The affected DCs expressed low level of CDla, CD80, CD86 and HLA-DR. TNF-α promoted immature DCs differentiating to mature DCs. When MM-MSCs were added, IL-12 secreted by DCs was decreased. On the anti-myeloma response of T cell affected by DCs, the apoptosis of U266 in without- MSC group, with ND-MSC group and with MM-MSC group were （ 70. 0 ± 5.0 ） %, （41.4 ± 5.7 ） % and （ 27.7 ± 5.6）%, respectively. Conclusions Differentiation, maturation and IL-12 secretion of dendritic cells were inhibited by MSCs of MM patients. Anti-myeloma response T cell supported by DCs could be inhibited by MSCs of MM patients.