Multiomics characterization of mesenchymal stromal cells cultured in monolayer and as aggregates.,Biotechnology and Bioengineering

当前位置： X-MOL 学术 › Biotechnol. Bioeng. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Multiomics characterization of mesenchymal stromal cells cultured in monolayer and as aggregates.
Biotechnology and Bioengineering ( IF 3.5 ) Pub Date : 2020-03-09 , DOI: 10.1002/bit.27317
Gilad Doron ₁ , Michail E Klontzas _{1,

2} , Athanasios Mantalaris ₁ , Robert E Guldberg _{3,

4,

5} , Johnna S Temenoff _{1,

3}

Affiliation

Mesenchymal stromal cells (MSCs) have failed to consistently demonstrate their therapeutic efficacy in clinical trials, due in part to variability in culture conditions used for their production. Of various culture conditions used for MSC production, aggregate culture has been shown to improve secretory capacity (a putative mechanism of action in vivo) compared with standard monolayer culture. The purpose of this study was to perform multiomics characterization of MSCs cultured in monolayer and as aggregates to identify aspects of cell physiology that differ between these culture conditions to begin to understand cellular-level changes that might be related to secretory capacity. Targeted secretome characterization was performed on multiple batches of MSC-conditioned media, while nontargeted proteome and metabolome characterization was performed and integrated to identify cellular processes differentially regulated between culture conditions. Secretome characterization revealed a reduction in MSC batch variability when cultured as aggregates. Proteome and metabolome characterization showed upregulation of multiple protein and lipid metabolic pathways, downregulation of several cytoskeletal processes, and differential regulation of extracellular matrix synthesis. Integration of proteome and metabolome characterization revealed individual lipid metabolites and vesicle-trafficking proteins as key features for discriminating between culture conditions. Overall, this study identifies several aspects of MSC physiology that are altered by aggregate culture. Further exploration of these processes and pathways is needed to determine their potential role in regulating cell secretory capacity.

中文翻译：

以单层和聚集体形式培养的间充质基质细胞的多组学表征。

间充质基质细胞 (MSC) 未能在临床试验中始终如一地证明其治疗功效，部分原因是用于其生产的培养条件存在差异。在用于 MSC 生产的各种培养条件中，与标准单层培养相比，聚集培养已被证明可以提高分泌能力（一种推定的体内作用机制）。本研究的目的是对单层培养和作为聚集体的 MSC 进行多组学表征，以确定这些培养条件之间不同的细胞生理学方面，以开始了解可能与分泌能力相关的细胞水平变化。对多批 MSC 条件培养基进行了靶向分泌组表征，而非靶向蛋白质组和代谢组的表征被执行和整合，以识别不同培养条件之间差异调节的细胞过程。分泌组表征显示，当作为聚集体培养时，MSC 批次变异性降低。蛋白质组和代谢组表征显示多种蛋白质和脂质代谢途径的上调、几种细胞骨架过程的下调以及细胞外基质合成的差异调节。蛋白质组和代谢组特征的整合揭示了个体脂质代谢物和囊泡运输蛋白是区分培养条件的关键特征。总的来说，这项研究确定了聚合培养改变的 MSC 生理学的几个方面。

更新日期：2020-03-09

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11