骨髓瘤患者骨髓间充质干细胞可异常影响骨髓瘤细胞株的趋化功能

摘要

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Transwel 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Transwel 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Transwel 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Transwel 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 cels from multiple myeloma patients present a variety of abnormalities, it is unclear how these abnormal mesenchymal stem cels influence the chemotactic function of myeloma cel lines. OBJECTIVE:To investigate thein vitro effects of bone marrow mesenchymal stem cels from normal donors versus multiple myeloma patients on the chemotactic capacity of myeloma cel lines. METHODS:In vitro cultured bone marrow mesenchymal stem cels derived from either normal donors (N-MSCs group) or newly-diagnosed multiple myeloma patients (MN-MSCs group) were directly co-cultured with U266 cels, in the presence or absence of bortezomib; and then harvested U266 cels were assayed for Transwel migration and mRAN expression of chemotaxis-related genes. U266 Transwel 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 cels harvested from MN-MSCs group showed increased spontaneous Transwel migration and up-regulated CCR1 mRNA level than those from N-MSCs group (P < 0.05), whatever bortezomib was present or not. However, there was no evident difference between U266 cel Transwel 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 cels derived from multiple myeloma patients, which can modulate the chemotactic migration of myeloma cel lines when they directly interact with each other.