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饮食组成可短暂调节人脐带血来源间充质干细胞的增殖和潜能特性。

Diet composition transiently modulates proliferative and potency features of human cord blood-derived mesenchymal stem cells.

作者信息

Ragni Enrico, Parazzi Valentina, Crosti Mariacristina, Moro Monica, Giordano Rosaria, Lazzari Lorenza

机构信息

Cell Factory, Unit for Cellular Therapy and Cryobiology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy.

Istituto Nazionale Genetica Molecolare "Romeo ed Enrica Invernizzi" (INGM), Milano, Italy.

出版信息

Int J Biochem Cell Biol. 2014 Oct;55:269-78. doi: 10.1016/j.biocel.2014.09.017. Epub 2014 Sep 22.

Abstract

Mesenchymal stem cells (MSC) emerged in the last few years as a promise in regenerative medicine and have been actively tested in several clinical trials worldwide. However, the lack of common standards and a precise definition of MSC preparations remain a major obstacle in research and application. In this study, we compared the effects during culture of two different MSC commercial media (aMEM and SPE-IV) on the proliferative capacities, phenotypic and molecular features in human cord blood derived-MSC lines. Moreover, as miRNA are markers of stem cell multipotency and regulators of somatic cell reprogramming, we performed a miRNome analysis in both conditions. As a result, we observed that SPE-IV promoted a faster growth and modulated stemness and proliferation associated genes such as PDGFRB, p16 and p21. Notably, in aMEM miR-335 and miR-302b, both proposed as putative stemness markers, were upregulated together with miRNAs reported to decrease adipo- and osteogenesis confirming the observed reduced differentiation potential after growth in this condition. Intriguingly, phenotypic divergences were entirely due to culturing conditions and, most importantly, completely transitory since, after medium switch, the cells were able to revert their signatures. Thus, it emerges as crucial keeping constant the experimental settings, starting from culturing conditions, to avoid misleading characterization of stemness and/or potency markers when the eventual goal is unequivocal definition of such parameters for future clinical choice.

摘要

间充质干细胞(MSC)在过去几年中成为再生医学领域的一大希望,并已在全球多项临床试验中得到积极测试。然而,缺乏通用标准以及对MSC制剂的精确定义仍然是研究和应用中的主要障碍。在本研究中,我们比较了两种不同的MSC商业培养基(α-MEM和SPE-IV)在培养过程中对人脐带血来源的MSC系的增殖能力、表型和分子特征的影响。此外,由于miRNA是干细胞多能性的标志物和体细胞重编程的调节因子,我们在两种条件下都进行了miRNome分析。结果,我们观察到SPE-IV促进了更快的生长,并调节了与干性和增殖相关的基因,如血小板衍生生长因子受体β(PDGFRB)、p16和p21。值得注意的是,在α-MEM中,均被认为是假定干性标志物的miR-335和miR-302b上调,同时有报道称一些miRNA会降低脂肪生成和成骨作用,这证实了在此条件下生长后观察到的分化潜能降低。有趣的是,表型差异完全是由于培养条件所致,最重要的是,这种差异是完全暂时的,因为在更换培养基后,细胞能够恢复其特征。因此,从培养条件开始,保持实验设置的恒定至关重要,以避免在最终目标是明确界定这些参数以供未来临床选择时,对干性和/或潜能标志物进行误导性的表征。

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