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Graphene Potentiates the Myocardial Repair Efficacy of Mesenchymal Stem Cells by Stimulating the Expression of Angiogenic Growth Factors and Gap Junction Protein

机译:石墨烯通过刺激血管生成生长因子和间隙连接蛋白的表达增强间充质干细胞的心肌修复功效。

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摘要

Stem cell therapy has emerged as a potential modality for myocardial infarction treatment. Mesenchymal stem cells (MSCs) exert reparative actions in the injured myocardium mainly through the secretion of paracrine factors. In addition, the overexpression of connexin 43 (Cx43), a gap junction protein, promotes cardiac repair and function restoration. It is known that MSCs in a spheroid form, which have enhanced cell-cell interaction, exhibit enhanced expression of paracrine factors and Cx43. However, cell-extracellular matrix (ECM) interactions, which also contribute to growth factor expression, are very limited in MSC spheroids. Reduced graphene oxide (RGO) shows high affinity toward ECM proteins, such as fibronectin (FN), and high electrical conductivity. In this study, by incorporating FN-adsorbed RGO flakes into MSC spheroids, it is possible to enhance the cell-ECM interactions and, subsequently, the paracrine factor expression in the MSCs in spheroids. Cx43 is also upregulated likely due to the enhanced paracrine factor expression and electrical conductivity of RGO. The injection of MSC-RGO hybrid spheroids into the infarcted hearts enhances cardiac repair compared with the injection of RGO flakes or MSC spheroids. This study demonstrates that RGO can effectively improve the therapeutic efficacy of MSCs for ischemic heart diseases.
机译:干细胞治疗已成为心肌梗死治疗的潜在方式。间充质干细胞(MSC)主要通过分泌旁分泌因子在受损的心肌中发挥修复作用。此外,缝隙连接蛋白连接蛋白43(Cx43)的过表达促进心脏修复和功能恢复。已知呈球状的MSC具有增强的细胞间相互作用,其旁分泌因子和Cx43的表达增强。但是,在MSC球体中,细胞-细胞外基质(ECM)相互作用(也有助于生长因子表达)非常有限。还原的氧化石墨烯(RGO)对ECM蛋白(如纤连蛋白(FN))显示出高亲和力,并具有高电导率。在这项研究中,通过将FN吸附的RGO薄片掺入MSC球体中,可以增强细胞-ECM相互作用,进而增强MSC中球体中旁分泌因子的表达。由于旁分泌因子的表达和RGO的电导率提高,Cx43也可能被上调。与RGO薄片或MSC球体的注射相比,将MSC-RGO混合球体注射到梗塞的心脏中可增强心脏修复。这项研究表明,RGO可以有效提高MSC对缺血性心脏病的治疗效果。

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  • 来源
    《Advanced Functional Materials》 |2015年第17期|2590-2600|共11页
  • 作者单位

    Seoul Natl Univ, Sch Chem & Biol Engn, Seoul 151744, South Korea;

    Chonnam Natl Univ Hosp, Dept Cardiol, Gwangju 501757, South Korea;

    Seoul Natl Univ, Interdisciplinary Program Bioengn, Seoul 151744, South Korea;

    Chonnam Natl Univ Hosp, Dept Cardiol, Gwangju 501757, South Korea;

    Seoul Natl Univ, Dept Chem, Seoul 151747, South Korea;

    Seoul Natl Univ, Sch Chem & Biol Engn, Seoul 151744, South Korea;

    Chonnam Natl Univ Hosp, Dept Cardiol, Gwangju 501757, South Korea;

    Seoul Natl Univ, Dept Chem, Seoul 151747, South Korea;

    Chonnam Natl Univ Hosp, Dept Cardiol, Gwangju 501757, South Korea;

    Seoul Natl Univ, Sch Chem & Biol Engn, Seoul 151744, South Korea|Seoul Natl Univ, Interdisciplinary Program Bioengn, Seoul 151744, South Korea|Seoul Natl Univ, Engn Res Inst, BioMAX Inst, Inst Chem Proc, Seoul 151744, South Korea;

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