骨髓基质干细胞靶向胶质瘤迁徙的研究

The experiment study on mesenchymal stem cell tropism to malignant glioma

目的探讨骨髓基质于细胞（MSCs）向胶质瘤迁徙的能力及其分布模式。方法应用纳米超顺磁性氧化铁粒子（SPIO）和增强型绿色荧光蛋白（EGFP）双重标记大鼠MSCs，Transwell系统定量分析MSCs的迁徙能力。将标记的MSCs经静脉注射人胶质瘤荷瘤大鼠体内，普鲁士蓝和荧光染色检测MSCs靶向颅内胶质瘤迁移的分布模式。结果与生理盐水或正常脑组织溶解物比较，F98胶质瘤细胞和F98胶质瘤溶解物显著诱导MSCs向其迁徙（P〈0．01）。F98胶质瘤细胞显著刺激MSCs的迁徙（三倍于对照组），而F98胶质瘤溶解物具有最强的诱导MSCs迁徙的能力（五倍于对照组）。移植MSCs后第7天，SPIO／EGFP双标细胞散在分布于肿瘤中；第14天，绝大多数标记的MSCs位于肿瘤和正常脑组织之间沿肿瘤边界分布。结论系统移植的MSCs高度特异性地向颅内胶质瘤“归巢”,呈时空分布模式。

Objective To delineate the pattern of mesenchymal stem cells （MSCs） distribution in glioma after systematical injection, and to track the migration and incorporation of magnetically labeled MSCs. Methods Fisher344 rats MSCs were co-labeled with superparamagnetic iron oxide nanoparticles （SPIO） and enhanced green fluorescence protein （EGFP）. The tropism capacity of MSCs was quantitatively assayed by Transwell system in vitro. Seven and 14 days after systematic administration of labeled MSCs,the distribution patterns of MSCs in glioma burdened rats were examined by Prussian blue and fluorescence staining. Results F98 cells and lysis of F98 glioma significantly stimulated the directional migration of the MSCs compared to saline or normal brain tissue extract （ P 〈 0. 01 ）. As expected glioma cell lines （ F98 cell） significantly stimulated MSCs migration （ up to 3-fold compared to the control） but interestingly,lysis of F98 induced the highest chemotactic response （up to 5-fold）. At 7th day after MSCs transplantation, the SPIO/EGFP co-labeled cells distributed throughout the tumor, while at 14th day, most of labeled MSCs were found at the border between tumor and normal parenchyma. Condusion Systemically transplanted MSCs ＂home＂ to glioma with high specificity with a temporal-spatial pattern.