Zhang Bo, Kasoju Naresh, Li Qiongfang, Ma Jinmin, Yang Aidong, Cui Zhanfeng, Wang Hui, Ye Hua
Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, UK.
Department of Engineering Science, University of Oxford, Oxford, UK.
Int J Stem Cells. 2019 Mar 30;12(1):84-94. doi: 10.15283/ijsc18102.
The International Society for Cellular Therapy (ISCT) proposed a set of minimal markers for identifying human mesenchymal stromal cells (hMSCs) in 2007. Since then, with the growing interest of better characterising hMSCs, various additional surface markers have been proposed. However, the impact of how culture conditions, in particular, the culture surface, vary the expression of hMSC markers was overlooked.
In this study, we utilized the RNA sequencing data on hMSCs cultured on different surfaces to investigate the variation of the proposed hMSC biomarkers. One of the three ISCT proposed positive biomarker, CD90 was found to be significantly down regulated on hMSCs culture on fibrous surfaces when compared to flat surfaces. The detected gene expression values for 177 hMSCs biomarkers compiled from the literature are reported here. Correlation and cluster analysis revealed the existence of different biomarker communities that displayed a similar expression profile. We found a list of hMSCs biomarkers which are the least sensitive to a change in surface properties and another list of biomarkers which are found to have high sensitivity to a change in surface properties.
This study demonstrated that substrate properties have paramount effect on altering the expressions of hMSCs biomarkers and the proposed list of substrate-stable and substrate-sensitive biomarkers would better assist in the population characterisation. However, proteomic level analysis would be essential to confirm the observations noted.
国际细胞治疗协会(ISCT)于2007年提出了一套用于鉴定人骨髓间充质干细胞(hMSCs)的最小标志物。自那时起,随着对更好地表征hMSCs兴趣的增加,人们提出了各种额外的表面标志物。然而,培养条件,特别是培养表面,如何改变hMSC标志物表达的影响却被忽视了。
在本研究中,我们利用在不同表面培养的hMSCs的RNA测序数据来研究所提出的hMSC生物标志物的变化。与平坦表面相比,在纤维表面培养的hMSCs上,ISCT提出的三个阳性生物标志物之一CD90被发现显著下调。本文报告了从文献中汇编的177种hMSCs生物标志物的检测基因表达值。相关性和聚类分析揭示了存在具有相似表达谱的不同生物标志物群落。我们发现了一组对表面性质变化最不敏感的hMSCs生物标志物,以及另一组对表面性质变化高度敏感的生物标志物。
本研究表明,底物性质对改变hMSCs生物标志物的表达具有至关重要的影响,所提出的底物稳定和底物敏感生物标志物列表将更好地协助群体表征。然而,蛋白质组水平分析对于确认所观察到的结果至关重要。