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缺氧和常氧条件下培养的内皮样细胞外囊泡的 miRNA 谱的选择性加载和变化。

Selective Loading and Variations in the miRNA Profile of Extracellular Vesicles from Endothelial-like Cells Cultivated under Normoxia and Hypoxia.

机构信息

Stem Cells Basic Biology Laboratory, Instituto Carlos Chagas-ICC-FIOCRUZ/PR, Rua Professor Algacyr Munhoz Mader, 3775, Curitiba 81350-010, PR, Brazil.

Gene Expression Regulation Laboratory, Instituto Carlos Chagas-ICC-FIOCRUZ/PR, Rua Professor Algacyr Munhoz Mader, 3775, Curitiba 81350-010, PR, Brazil.

出版信息

Int J Mol Sci. 2022 Sep 2;23(17):10066. doi: 10.3390/ijms231710066.

DOI:10.3390/ijms231710066
PMID:36077462
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9456085/
Abstract

Endothelial-like cells may be obtained from CD133 mononuclear cells isolated from human umbilical cord blood (hUCB) and expanded using endothelial-inducing medium (E-CD133 cells). Their use in regenerative medicine has been explored by the potential not only to form vessels but also by the secretion of bioactive elements. Extracellular vesicles (EVs) are prominent messengers of this paracrine activity, transporting bioactive molecules that may guide cellular response under different conditions. Using RNA-Seq, we characterized the miRNA content of EVs derived from E-CD133 cells cultivated under normoxia (N-EVs) and hypoxia (H-EVs) and observed that changing the O status led to variations in the selective loading of miRNAs in the EVs. In silico analysis showed that among the targets of differentially loaded miRNAs, there are transcripts involved in pathways related to cell growth and survival, such as FoxO and HIF-1 pathways. The data obtained reinforce the pro-regenerative potential of EVs obtained from E-CD133 cells and shows that fine tuning of their properties may be regulated by culture conditions.

摘要

内皮样细胞可从人脐血（hUCB）分离的 CD133 单核细胞中获得，并使用内皮诱导培养基（E-CD133 细胞）进行扩增。通过其形成血管的潜力以及分泌生物活性元素，人们探索了它们在再生医学中的应用。细胞外囊泡（EVs）是这种旁分泌活性的主要信使，它们运输生物活性分子，这些分子可能在不同条件下指导细胞反应。通过 RNA-Seq，我们对在常氧（N-EVs）和低氧（H-EVs）条件下培养的 E-CD133 细胞衍生的 EVs 的 miRNA 含量进行了表征，并观察到改变 O 状态会导致 EVs 中 miRNA 的选择性加载发生变化。计算分析表明，在差异加载 miRNA 的靶标中，有参与与细胞生长和存活相关途径的转录本，如 FoxO 和 HIF-1 途径。获得的数据增强了 E-CD133 细胞衍生的 EVs 的促再生潜力，并表明可以通过培养条件调节其特性的精细调整。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/731e/9456085/ba632bfa1f76/ijms-23-10066-g005.jpg
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