背景:多发性骨髓瘤患者骨髓微环境中间充质干细胞有多种异常,但异常的间充质干细胞对骨髓瘤细胞的趋化功能影响目前仍不清楚。目的:比较正常人与多发性骨髓瘤患者骨髓间充质干细胞在体外对骨髓瘤细胞株趋化迁移的影响。方法:体外培养的正常人骨髓间充质干细胞或初诊骨髓瘤患者骨髓间充质干细胞,在有或无硼替佐米条件下,分别与骨髓瘤细胞株U266细胞直接共培养,比较U266细胞的Transwell迁移率、定量PCR检测mRNA的表达水平。同时还检测U266细胞对正常人骨髓间充质干细胞或骨髓瘤患者骨髓间充质干细胞培养液上清的Transwell迁移情况。结果与结论:正常人骨髓间充质干细胞或骨髓瘤患者骨髓间充质干细胞与U266细胞直接共培养后,两组骨髓瘤细胞的趋化特性有区别,表现为骨髓瘤患者骨髓间充质干细胞组的U266细胞基础Transwell迁移率高、CCR1的表达水平高(P均〈0.05)。硼替佐米处理U266细胞后并不能消除两组的的区别。然而,U266细胞对正常人骨髓间充质干细胞或骨髓瘤患者骨髓间充质干细胞培养液上清的Transwell迁移并没有明显区别。结果提示骨髓瘤患者骨髓间充质干细胞本身存在一些内在缺陷,在与骨髓瘤细胞株U266相互作用过程中,可以影响U266的体外趋化功能,并且这一影响主要是通过骨髓间充质干细胞与骨髓瘤细胞直接相互作用引起的。
BACKGROUND: Although bone marrow mesenchymal stem cells from multiple myeloma patients present a variety of abnormalities, it is unclear how these abnormal mesenchymal stem cells influence the chemotactic function of myeloma cell lines. OBJECTIVE: To investigate the in vitro effects of bone marrow mesenchymal stem cells from normal donors versus multiple myeloma patients on the chemotactic capacity of myeloma cell lines. METHODS: In vitro cultured bone marrow mesenchymal stem cells derived from either normal donors(N-MSCs group) or newly-diagnosed multiple myeloma patients(MN-MSCs group) were directly co-cultured with U266 cells, in the presence or absence of bortezomib; and then harvested U266 cells were assayed for Transwell migrationand m RAN expression of chemotaxis-related genes. U266 Transwell migration to conditioned medium derived from either N-MSCs or MN-MSCs was also tested. RESULTS AND CONCLUSION: After co-cultured with N-MSCs or MN-MSCs, U266 cells harvested from MN-MSCs group showed increased spontaneous Transwell migration and up-regulated CCR1 m RNA level than those from N-MSCs group(P〈0.05), whatever bortezomib was present or not. However, there was no evident difference between U266 cell Transwell migration to conditioned medium derived from either MM-MSCs group or N-MSCs group. Our study implies that there may be some intrinsic aberrance in bone marrow mesenchymal stem cells derived from multiple myeloma patients, which can modulate the chemotactic migration of myeloma cell lines when they directly interact with each other.