骨髓间充质干细胞向脑胶质瘤趋向性的初步研究

背景骨髓间充质干细胞(MSCs)是存在于骨髓中的非造血类干细胞,具有自我更新及多向分化潜能.在大鼠脑外伤模型中的迁移能力已得到证实,而其对于脑胶质瘤的趋向性的研究尚处于初期.本实验通过将标记的MSCs移植到大鼠脑胶质瘤模型体内,观察它的迁移情况.方法采用全骨髓细胞培养法,利用MSCs的贴壁生长及可在体外长期培养的特性,获取纯化的MSCs.采用流式细胞术鉴定其表面抗原及细胞周期.在处于对数生长期的MSCs培养皿中加入BrdUrd(终浓度10μg/mL),培养24～48 h后进行移植.采用立体定向技术建立大鼠脑胶质瘤模型,3 d后移植标记好的MSCs在大脑半球组,BrdUrd标记的MSCs被注入大鼠脑胶质瘤模型肿瘤对侧大脑;在颈内动脉组,BrdUrd标记的MSCs被注入大鼠脑胶质瘤模型肿瘤同侧的颈内动脉.分别以BrdUrd标记的3T3细胞作为对照组.2周后,处死大鼠取脑组织制作病理切片,进行抗BrdUrd免疫组化及免疫荧光染色,观察MSCs的迁移情况.结果全骨髓培养法获得了纯化的MSCs.移植到脑组织及颈内动脉的BrdUrd标记的MSCs表现出了明显的向脑胶质瘤迁移的特性.在大脑半球组,MSCs主要集中在肿瘤与正常脑组织的交界部位,在瘤内只有少量分布.在颈内动脉组,MSCs主要分布于肿瘤内部,在肿瘤与正常脑组织的交界位置有少量分布.结论MSCs具有明显的向脑胶质瘤迁移的特性,同时亦可通过血脑屏障,有可能成为胶质瘤基因治疗的理想载体.

The preliminary study on the bone marrow-derived mesenchymal stem cells migrating toward glioma

Background Bone marrow-derived mesenchymal stem cells (MSCs) have been reported to have the ability of migrating after transplantation into rat model of traumatic brain injury. In this study, MSCs' characteristic of tropism for intracranial glioma was explored following being labeled and transplanted into brain and blood of glioma-bearing rats. Methods Cellulae medullares were cultured to get pure MSCs. The cell surface antigen and cell cycle of MSCs were detected to confirm their identity by flow cytometry. MSCs were marked with BrdU and then were injected into contralateral brain or collateral internal carotid artery of rats bearing glioma. 2 weeks later, the brains were resected and pathological sections were made. Immunohistochemistry and immunofluorescence technology were performed to detect MSCs. Results MSCs displayed extensive tropism for intracranial glioma. MSCs which were injected in the contralateral brain of the glioma scattered densely in the juncture between brain tissue and tumor and there were a few MSCs in the glioma; MSCs which were injected into the collateral internal carotid artery scattered widespread in the glioma and there were a few MSCs in the juncture area. Conclusions MSCs have the ability to migrating toward glioma and penetrating blood brain barrier. MSCs may be ideal gene therapy vehicles against glioma.