颈内动脉移植骨髓间充质干细胞向C6胶质瘤的趋化迁移

目的探讨经颈内动脉移植的骨髓间充质干细胞(BMSC)向C6胶质瘤的趋化迁移能力及小剂量S缓激肽对其影响。方法密度梯度离心法分离BMSCs,体外培养、传代纯化。利用Transwell侵袭小室建立体外趋化迁移模型。立体定向方法建立大鼠C6胶质瘤模型。用BrdU标记BMSCs,经荷瘤侧颈内动脉灌注,观察其向C6胶质瘤组织的趋化能力以及在使用小剂量缓激肽后对其的影响。结果通过密度梯度离心法传至第3代获得了纯化的MSCs。体外模型中BMSCs可通过聚碳酸酯膜向下室内的C6细胞迁移。经颈内动脉灌注后BMSCs可以存活,并表现出了向脑胶质瘤趋化迁移的特性。分布区域主要位于肿瘤内部,在肿瘤与正常脑组织的交界位置亦有分布。使用小剂量缓激肽可以明显增加BMSCs通过血肿瘤屏障的数量。结论BMSCs具有通过血肿瘤屏障向C6胶质瘤趋化迁移的能力,经颈内动脉灌注是其有效的移植途径,小剂量缓激肽选择性开放血肿瘤屏障有助于BMSCs趋化迁移进入C6胶质瘤组织。

The Tropism of Bone Marrow-derived Mesenchymal Stem Cells for Intracranial Glioma after Being Transplanted through Internal Carotid Artery

Objectives To investigate the tropism and migration of bone marrow-derived mesenchymal stem cells (BMSCs) transplanted through internal carotid artery for C6 glioma and the influence of low dose of bradykinin (BK) on it. Methods BMSCs were isolated, cultured, passaged and purified in vitro by density gradient centrifugation method. Using Transwell inserts technique, we established in vitro model to study the tropism of BMSCs for C6 glioma. The rat C6 glioma model was established by stereotactic procedure. After being marked with BrdU, BMSCs were injected into collateral internal carotid artery of rats bearing glioma to study their tropism for C6 glioma in vivo and the influence of low dose of BK on it. Results BMSCs were successively subcultured and purified by density gradient centrifugation method. In vitro model showed that BMSCs can migrate through the polycarbonate filter toward C6 cells in the lower chamber. After being injected into internal carotid artery, BMSCs could survive in the brain of rats bearing glioma and showed extensive tropism for C6 glioma. BMSCs scattered in glioma and the juncture area between glioma and normal brain tissue. Low dose of BK can significantly increase the amount of BMSCs migrating through blood-tumor barrier. Conclusion BMSCs have the ability to penetrate blood tumor barrier and migrate toward C6 glioma, infusion through internal carotid artery is an effective way for their transplantation, and low dose of BK can help BMSCs to migrate into C6 glioma.