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Exosomes Secreted from Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cells Accelerate Skin Cell Proliferation

机译:从诱导多能干细胞衍生的间充质干细胞分泌的外泌体加速皮肤细胞增殖

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摘要

Induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSCs) serve as a unique source for cell therapy. We investigated whether exosomes from iMSCs promote the proliferation of human keratinocytes (HaCaT) and human dermal fibroblasts (HDFs). iPSCs were established from human Wharton’s jelly MSCs and were allowed to differentiate into iMSCs. Exosomes were collected from the culture supernatant of MSCs (MSC-exo) and iMSCs (iMSC-exo), and their characteristics were investigated. Both exosome types possessed basic characteristics of exosomes and were taken up by skin cells in vitro and in vivo. A significant increase in HaCaT proliferation was observed with iMSC-exo, although both exosomes increased the viability and cell cycle progression in HaCaT and HDFs. No significant difference was observed in the closure of wound scratch and the expression of reparative genes between cells treated with the two exosome types. Both exosomes enhanced the secretion of collagen in HaCaT and HDFs; however, an increase in fibronectin level was observed only in HaCaT, and this effect was better with iMSC-exo treatment. Only iMSC-exo increased the phosphorylation of extracellular signal-regulated kinase (ERK)-1/2. Our results indicate that iMSC-exo promote the proliferation of skin cells by stimulating ERK1/2 and highlight the application of iMSCs for producing exosomes.
机译:诱导多能干细胞(iPSC)衍生的间充质干细胞(iMSCs)是细胞治疗的独特来源。我们调查了来自iMSC的外泌体是否促进人角质形成细胞(HaCaT)和人皮肤成纤维细胞(HDFs)的增殖。 iPSC是从沃顿商学院的果冻MSC建立的,可以分化为iMSC。从MSC(MSC-exo)和iMSC(iMSC-exo)的培养上清液中收集外来体,并研究它们的特性。两种外泌体类型都具有外泌体的基本特征,并且在体外和体内都被皮肤细胞吸收。 iMSC-exo观察到HaCaT增殖显着增加,尽管两种外泌体均增加了HaCaT和HDFs的活力和细胞周期进程。在两种外泌体类型处理的细胞之间,在伤口划痕的闭合和修复基因的表达方面未观察到显着差异。两种外泌体均增强了HaCaT和HDFs中胶原蛋白的分泌。但是,仅在HaCaT中观察到了纤连蛋白水平的增加,并且用iMSC-exo治疗效果更好。只有iMSC-exo增加了细胞外信号调节激酶(ERK)-1/2的磷酸化。我们的结果表明,iMSC-exo通过刺激ERK1 / 2促进皮肤细胞的增殖,并突出了iMSCs在生产外泌体中的应用。

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