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细胞扩增与炎症对人脂肪组织来源间充质基质细胞免疫生物学的影响

The Impact of Cell-Expansion and Inflammation on The Immune-Biology of Human Adipose Tissue-Derived Mesenchymal Stromal Cells.

作者信息

Buyl Karolien, Merimi Makram, Rodrigues Robim M, Moussa Agha Douâa, Melki Rahma, Vanhaecke Tamara, Bron Dominique, Lewalle Philippe, Meuleman Nathalie, Fahmi Hassan, Rogiers Vera, Lagneaux Laurence, De Kock Joery, Najar Mehdi

机构信息

Department of In Vitro Toxicology and Dermato-Cosmetology, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels, Belgium.

Laboratory of Experimental Hematology, Institut Jules Bordet, Université Libre de Bruxelles (ULB), 121 Boulevard de Waterloo, 1000 Bruxelles, Belgium.

出版信息

J Clin Med. 2020 Mar 4;9(3):696. doi: 10.3390/jcm9030696.

Abstract

: As a cell-based therapeutic, AT-MSCs need to create an immuno-reparativeenvironment appropriate for tissue repair. In the presence of injury, MSCs may have to proliferate and face inflammation. Clinical application requires repeated administrations of a high number of cellswith a well-established immune profile. : We have established an immuno-comparative screening by determining the expression of 28 molecules implicated in immune regulation. This screening was performed during cell-expansion and inflammatory priming of AT-MSCs. : Our study confirms that AT-MSCs are highly expandable and sensitive to inflammation. Both conditions have substantially modulated the expression of a panel of immunological marker. Specifically, CD34 expression was substantially decreased upon cell-passaging. HLA-ABC, CD40 CD54, CD106, CD274 and CD112 were significantly increased by inflammation. In vitro cell-expansion also significantly altered the expression profile of HLA-DR, CD40, CD62L, CD106, CD166, HLA-G, CD200, HO-1, CD155 and ULBP-3. : This study points out the response and characteristics of MSCs following expansion and inflammatory priming. It will strength our knowledge about the molecular mechanisms that may improve or hamper the therapeutic potential of MSCs. These immunological changes need to be further characterized to guarantee a safe cellular product with consistent quality and high therapeutic efficacy.

摘要

作为一种基于细胞的疗法,脂肪间充质干细胞(AT-MSCs)需要营造一个适合组织修复的免疫修复环境。在存在损伤的情况下,间充质干细胞可能必须增殖并面对炎症。临床应用需要多次给予大量具有明确免疫特征的细胞。

我们通过测定28种与免疫调节相关分子的表达建立了免疫比较筛选。该筛选在脂肪间充质干细胞的细胞扩增和炎性预处理过程中进行。

我们的研究证实,脂肪间充质干细胞具有高度可扩展性且对炎症敏感。这两种情况都显著调节了一组免疫标志物的表达。具体而言,细胞传代后CD34表达大幅下降。炎症使HLA-ABC、CD40、CD54、CD106、CD274和CD112显著增加。体外细胞扩增也显著改变了HLA-DR、CD40、CD62L、CD106、CD166、HLA-G、CD200、HO-1、CD155和ULBP-3的表达谱。

这项研究指出了间充质干细胞在扩增和炎性预处理后的反应及特征。它将增强我们对可能改善或阻碍间充质干细胞治疗潜力的分子机制的认识。这些免疫变化需要进一步表征,以确保获得质量一致且治疗效果高的安全细胞产品。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c5ce/7141238/0d09b99bd5a3/jcm-09-00696-g001.jpg

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