摘要： 目的：研究氧化石墨烯（graphene oxide, GO）对骨髓间充质干细胞 (bone marrow-derived mesenchymal stem cells, BMSCs) 迁移能力的影响及相关机制，为氧化石墨烯在骨组织工程中的应用提供实验依据。方法：利用静电纺丝技术制备掺杂不同浓度GO的聚乳酸-羟基乙酸共聚物[poly (lactic-co-glycolic acid), PLGA]纤维支架，利用扫描电镜观察支架形貌，利用CCK-8、Transwell小室、划痕实验以及定量PCR（Quantitative real time polymerase chain reaction，qPCR）观察GO对大鼠BMSCs的细胞活性、迁移能力和相关基因表达的影响。结果：所制备的纤维支架具有多孔的空间结构，有利于细胞的迁移；随着GO浓度升高，纤维直径有所下降；0.25wt%和0.5wt%的GO掺杂表现出了良好的生物相容性，促进了BMSCs的迁移并且上调了PI3K、Akt、MMP2和MMP9的基因表达，当GO浓度上升至1.0wt%时，该促进作用有所下降。结论：GO可以通过激活PI3K/Akt/MMPs信号通路促进BMSCs的迁移。

关键词: 骨组织工程, 氧化石墨烯, 细胞迁移, 信号通路

Abstract: Objective: The aim of the study was to evaluate the effects of graphene oxide (GO) on the migration ability of bone marrow-derived mesenchymal stem cells (BMSCs) and investigate the related mechanisms. Methods: Pure polylactic-co-glycolic acid (PLGA) and 0.25, 0.5, or 1.0wt% GO-PLGA fibrous scaffolds were prepared by electrospinning. Morphology of fibers and BMSCs adhered were observed by scanning electron microscope. Cell viability was examined by CCK-8 assay. The migration of BMSCs was evaluated by Transwell and cell wound healing assays. 1-, 4-, and 7- day after cell seeding, the expressions of PI3K、Akt、MMP2 and MMP9 were detected by qPCR. Results: All four groups showed a porous 3D structure. Incorporation of 0.5, and 1.0wt% GO reduced the diameter of fibers (P<0.05). BMSCs successfully adhered to the fibers after 12h. Incorporation of 1.0wt% GO showed a slight cytotoxicity, especially at 7th day (P<0.05). Incorporation of 0.25, and 0.5wt% GO enhanced the migration of BMSCs and promoted the expression of PI3K、Akt、MMP2 and MMP9 in a concentration-related pattern, and the trend was reversed at the concentration of 1.0 wt% (P<0.05). Conclusion: GO can promote the migration of BMSCs by activating PI3K/Akt/MMPs signaling pathways in a suitable concentration range.

中图分类号: 

• R782.4