Conditioned medium derived from FGF-2-modified GMSCs enhances migration and angiogenesis of human umbilical vein endothelial cells

作者：Shanshan Jin, Chengzhe Yang, Jia-Hui Huang, Lianlian Liu, Yu Zhang, Shutong Li, Liguo Zhang, Qinfeng Sun, Pishan Yang · 发表于：Stem Cell Research & Therapy · 年份：2020 · DOI：10.1186/s13287-020-1584-3 · 被引用次数：70 · 研究领域：Periodontal Regeneration and Treatments、Mesenchymal stem cell research、Wound Healing and Treatments

Abstract Background Angiogenesis plays an important role in tissue repair and regeneration, and conditioned medium (CM) derived from mesenchymal stem cells (MSC-CM) possesses pro-angiogenesis. Nevertheless, the profile and concentration of growth factors in MSC-CM remain to be optimized. Fibroblast growth factor-2 (FGF-2) has been proven to be an effective angiogenic factor. Thus, the aim of this study was to verify whether FGF-2 gene overexpression optimized CM from human gingival mesenchymal stem cells (hGMSCs) and whether such optimized CM possessed more favorable pro-angiogenesis effect. Methods First, FGF-2 gene-modified hGMSCs were constructed using lentiviral transfection technology (LV-FGF-2 + -hGMSCs) and the concentration of angiogenesis-related factors in LV-FGF-2 + -hGMSC-CM was determined by ELISA. Then, human umbilical vein endothelial cells (HUVECs) were co-cultured for 3 days with LV-FGF-2 + -hGMSC-CM, and the expression level of placenta growth factor (PLGF), stem cell factor (SCF), vascular endothelial growth factor receptor 2 (VEGFR2) in HUVECs were determined by qRT-PCR, western blot, and cellular immunofluorescence techniques. The migration assay using transwell and in vitro tube formation experiments on matrigel matrix was conducted to determine the chemotaxis and angiogenesis enhanced by LV-FGF-2 + -hGMSC-CM. Finally, NOD-SCID mice were injected with matrigel mixed LV-FGF-2 + -hGMSC-CM, and the plug sections were analyzed by immunohistochemistry stainin...