骨髓基质干细胞趋瘤性及神经分化潜能

Tropism of bone marrow stromal cells to glioma and their neural differentiation potential

目的:观察骨髓基质干细胞(bone marrow stromal cells,BMSCs)向脑胶质瘤的趋向性及在荷瘤大鼠脑内的分化,初步探讨其机制。方法:培养BMSCs后,在体外应用显微镜直接观察及Transwell试验检测BMSCs向胶质瘤细胞及血管内皮细胞生长因子(VEGF)、表皮生长因子(EGF)、碱性成纤维细胞生长因子(b-FGF)、血小板源性生长因子(PDGF)等的迁移特性,免疫荧光方法检测其在颅内向脑胶质瘤迁移的情况。在体外诱导条件下,观察BMSCs的分化;BMSCs移植到脑荷瘤大鼠脑内15 d后,免疫荧光方法检测其在体内的分化。结果:骨髓基质干细胞在体外表现出明显的向胶质瘤细胞及PDGF、EGF的迁移特性,在体内表现了明显的向脑内胶质瘤迁移的特性,并可迁移到肿瘤卫星灶周围。在体外诱导条件下BMSCs可分化为神经前体细胞(8.4%±3.5%)、神经元(53.7%±7.4%)及胶质细胞(22.3%±5.2%);在移植到荷瘤鼠脑内后,也可分化为神经前体细胞(8.3%±3.6%)、神经元(15.7%±4.3%)及胶质细胞(32.5%±7.2%),两者向神经元分化的比例存在差异(P<0.05),向神经前体细胞及胶质细胞的分化比例相似(P>0.05)。结论:骨髓基质干细胞有明显的胶质瘤趋瘤性,其向神经细胞分化的方向可能与其局部微环境有关。

Objective ：To observe the tropism of bone marrow stromal cells （BMSCs） to intracranial glioma and their differentiation in the brain of rats bearing glioma, and to investigate the corresponding mechanism. Methods：The in vitro tropism of cultured BMSCs to glioma cells, vascular endothelial growth factor （VEGF）, epidermal growth factor （EGF）, basic fibroblast growth factor（FGF）, platelet derived growth factor （PDGF） were observed under microscope and detected by performing Transwell experiment. The in vivo tropism of BMSCs to intracranial glioma was observed by immunofluorescence method. The differentiation of BMSCs was induced in vitro and observed. After BMSCs were transplanted in the brain of glioma-bearing rats for 15 days, their in vivo differentiation was observed by immunofluorescence staining. Results：BMSCs displayed obvious in vitro tropism to glioma, PDGF, and EGF and in vivo tropism to intracranial glioma. They could migrate to satellite lesions of glioma in vivo. BMSCs were induced to differentiate into neural progenitor cells （8.4% ±3.5% ）, neurons （53.7% ±7.4% ）, and astrocytes（22.3% ±5.2% ） in vitro. After being transplanted into the brain of glioma-bearing rats, they also differentiated into neural progenitor cells （ 8.3% ± 3.6% ）, neurons （ 15.7% ± 4.3% ） and astrocytes （32.5% ±7.2% ）. There was significant difference in the differentiation ratio to neurons between in vitro and in vivo experiments（P 〈 0. 05 ）, but the differentiation ratios to neural progenitor cells and astrocytes had no significant difference （ P 〉 0. 05 ）. Conclusion： BMSCs display extensive tropism to glioma. The direction of the differentiation of BMSCs may be related with local microenvironment.