《Journal of Oral and Maxillofacial Surgery》

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Graphene Oxide Enhances Migration of Bone Marrow-derived Mesenchymal Stem Cells via Activation of PI3K/Akt/MMPs Signaling Pathways

ZHENG Shang, XIE Jian, SU Jian-sheng   

  1. Department of Prosthodontics, School & Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai 200072, China
  • Online:2018-12-01 Published:2019-11-28

氧化石墨烯对骨髓间充质干细胞迁移影响的实验研究

郑 尚, 苏俭生   

  1. 上海牙组织修复与再生工程技术研究中心,同济大学口腔医学院·附属口腔医院口腔修复科,上海 200072
  • 通讯作者: 苏俭生,教授. E-mail: sjs@tongji.edu.cn
  • 作者简介:郑 尚(1992—),男,河南人,硕士研究生. E-mail: zs9527@hotmail.com
  • 基金资助:
    国家自然科学基金(81572114、81873715);上海市科学技术委员会项目(18441902100、 17140903600)

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.

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

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