Efficient scalable production of therapeutic microvesicles derived from human mesenchymal stem cells.

Efficient scalable production of therapeutic microvesicles derived from human mesenchymal stem cells.
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源自人间充质干细胞的治疗微泡的有效可扩展产生。

DOI:
10.1038/s41598-018-19211-6
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发表时间:
2018-01-19
期刊:
影响因子:
4.6
通讯作者:
Bang OY
Bang OY
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Cha JM;Shin EK;Sung JH;Moon GJ;Kim EH;Cho YH;Park HD;Bae H;Kim J;Bang OY

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细胞释放的微泡作为细胞间通讯的重要媒介,参与了许多生理事件。来自间充质干细胞(MSCs)的MVs含有来自细胞的各种旁分泌因子,这些因子主要有助于在许多临床试验中观察到其治疗效果。由于纳米级和双脂质层状囊泡具有与间充质干细胞相当的治疗效力,因此,间充质干细胞衍生的mv已成为再生医学的理想候选药物,并且由于其安全性的提高,比间充质干细胞输注治疗更受青睐。然而,获得足量mv的技术挑战限制了研究和临床应用的进一步进展。在加强间充质干细胞治疗能力的多项努力中,据报道很少有研究检验了间充质干细胞衍生的MV生产的规模。在这项研究中,我们使用一种简单有效的3d生物处理方法,成功地扩增了MSCs的MV分泌,与传统培养方法相比。在我们的动态3d培养中产生的msc衍生的mv含有许多治疗因子,如细胞因子和微rna,并在体外疗效评估中显示出其治疗效力。我们的研究结果可能促进msc衍生mv从实验台到床边的多样化应用,这需要mv的大规模生产。
Microvesicles (MVs) released by cells are involved in a multitude of physiological events as important mediators of intercellular communication. MVs derived from mesenchymal stem cells (MSCs) contain various paracrine factors from the cells that primarily contribute to their therapeutic efficacy observed in numerous clinical trials. As nano-sized and bi-lipid layered vesicles retaining therapeutic potency equivalent to that of MSCs, MSC-derived MVs have been in focus as ideal medicinal candidates for regenerative medicine, and are preferred over MSC infusion therapy with their improved safety profiles. However, technical challenges in obtaining sufficient amounts of MVs have limited further progress in studies and clinical application. Of the multiple efforts to reinforce the therapeutic capacity of MSCs, few studies have reportedly examined the scale-up of MSC-derived MV production. In this study, we successfully amplified MV secretion from MSCs compared to the conventional culture method using a simple and efficient 3D-bioprocessing method. The MSC-derived MVs produced in our dynamic 3D-culture contained numerous therapeutic factors such as cytokines and micro-RNAs, and showed their therapeutic potency in in vitro efficacy evaluation. Our results may facilitate diverse applications of MSC-derived MVs from the bench to the bedside, which requires the large-scale production of MVs.
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