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编码 SDF-1α 和 VEGF165 基因的质粒 DNA 的体外血管生成特性。

In Vitro Angiogenic Properties of Plasmid DNA Encoding SDF-1α and VEGF165 Genes.

机构信息

Kazan Federal University, Kazan, Russia.

Histograft, LLC, Moscow, Russia.

出版信息

Appl Biochem Biotechnol. 2020 Mar;190(3):773-788. doi: 10.1007/s12010-019-03128-5. Epub 2019 Sep 7.

Abstract

The stromal-derived factor-1 alpha (SDF-1α) and vascular endothelial growth factor (VEGF) play an important role in angiogenesis and exert a significant trophic function. SDF-1α is a chemoattractant for endothelial progenitor cells derived from bone marrow and promotes new blood vessel formation. VEGF regulates all types of vascular growth, stimulates angiogenesis, and is involved in the induction of lymphangiogenesis. The possibility of using these growth factors for regenerative medicine is currently under investigation. The angiogenic potential of a pBud-SDF-1α-VEGF165 bicistronic plasmid construct which simultaneously encodes VEGF165 and SDF-1α genes cDNA was evaluated in this study. The conditioned medium collected from HEK293T cells transfected with the pBud-SDF-1α-VEGF165 plasmid was shown to stimulate the formation of capillary-like structures by human umbilical vein-derived endothelial cells (HUVEC) on Matrigel and to increase the proliferative activity of these cells in vitro. Thus, the pBud-SDF-1α-VEGF165 plasmid exhibits angiogenic properties in cell cultures in vitro. As interest in the development of non-viral techniques for regenerative medicine increases, this plasmid which simultaneously expresses VEGF165 and SDF-1α may provide a platform for advanced methods of stimulating therapeutic angiogenesis.

摘要

基质细胞衍生因子-1α(SDF-1α)和血管内皮生长因子(VEGF)在血管生成中发挥重要作用,并具有显著的营养功能。SDF-1α 是骨髓来源的内皮祖细胞的趋化因子,促进新血管形成。VEGF 调节所有类型的血管生长,刺激血管生成,并参与淋巴管生成的诱导。目前正在研究这些生长因子在再生医学中的应用可能性。本研究评估了同时编码 VEGF165 和 SDF-1α 基因 cDNA 的 pBud-SDF-1α-VEGF165 双顺反子质粒构建体的血管生成潜力。转染 pBud-SDF-1α-VEGF165 质粒的 HEK293T 细胞的条件培养基显示出刺激人脐静脉来源的内皮细胞(HUVEC)在 Matrigel 上形成毛细血管样结构,并增加这些细胞的体外增殖活性。因此,pBud-SDF-1α-VEGF165 质粒在体外细胞培养中表现出血管生成特性。随着对再生医学中非病毒技术发展的兴趣增加,这种同时表达 VEGF165 和 SDF-1α 的质粒可能为刺激治疗性血管生成的先进方法提供平台。

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