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脂肪间充质基质/干细胞在细胞扩增和炎症预刺激后的免疫特性。

The Immunological Profile of Adipose Mesenchymal Stromal/Stem Cells after Cell Expansion and Inflammatory Priming.

机构信息

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

LBBES Laboratory, Genetics and Immune Cell Therapy Unit, Faculty of Sciences, University Mohammed Premier, Oujda 60000, Morocco.

出版信息

Biomolecules. 2024 Jul 15;14(7):852. doi: 10.3390/biom14070852.

DOI:10.3390/biom14070852
PMID:39062566
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11275169/
Abstract

BACKGROUND

AT-MSCs display great immunoregulatory features, making them potential candidates for cell-based therapy. This study aimed to evaluate the "RBC lysis buffer" isolation protocol and immunological profiling of the so-obtained AT-MSCs.

METHODS

We established an immune-comparative screening of AT-MSCs throughout in vitro cell expansion (PM, P1, P2, P3, P4) and inflammatory priming regarding the expression of 28 cell-surface markers, 6 cytokines/chemokines, and 10 TLR patterns.

FINDINGS

AT-MSCs were highly expandable and sensitive to microenvironment challenges, hereby showing plasticity in distinct expression profiles. Both cell expansion and inflammation differentially modulated the expression profile of CD34, HLA-DR, CD40, CD62L, CD200 and CD155, CD252, CD54, CD58, CD106, CD274 and CD112. Inflammation resulted in a significant increase in the expression of the cytokines , , , , , and . Depending on the culture conditions, the expression of the TLR pattern was distinctively altered with , , and being increased, whereas was downregulated. Protein network and functional enrichment analysis showed that several trophic and immune responses are likely linked to these immunological changes.

CONCLUSIONS

AT-MSCs may sense and actively respond to tissue challenges by modulating distinct and specific pathways to create an appropriate immuno-reparative environment. These mechanisms need to be further characterized to identify and assess a molecular target that can enhance or impede the therapeutic ability of AT-MSCs, which therefore will help improve the quality, safety, and efficacy of the therapeutic strategy.

摘要

背景

脂肪间充质干细胞(AT-MSCs)具有强大的免疫调节功能,使其成为细胞治疗的潜在候选者。本研究旨在评估“红细胞裂解缓冲液”分离方案以及由此获得的 AT-MSCs 的免疫特性。

方法

我们通过体外细胞扩增(PM、P1、P2、P3、P4)和炎症预刺激,对 28 种细胞表面标志物、6 种细胞因子/趋化因子和 10 种 TLR 模式进行了免疫比较筛选。

结果

AT-MSCs 具有高度的可扩展性和对微环境挑战的敏感性,因此在不同的表达谱中表现出可塑性。细胞扩增和炎症均会导致 CD34、HLA-DR、CD40、CD62L、CD200 和 CD155、CD252、CD54、CD58、CD106、CD274 和 CD112 的表达谱发生差异调节。炎症导致细胞因子 、 、 、 、 和 的表达显著增加。根据培养条件的不同,TLR 模式的表达也明显改变, 、 和 增加,而 则下调。蛋白质网络和功能富集分析表明,几种营养和免疫反应可能与这些免疫变化相关。

结论

AT-MSCs 可以通过调节不同的特定途径来感知和主动响应组织挑战,从而创造适当的免疫修复环境。需要进一步研究这些机制,以确定和评估可以增强或阻碍 AT-MSCs 治疗能力的分子靶点,从而有助于提高治疗策略的质量、安全性和疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0b4/11275169/9acbd167a54d/biomolecules-14-00852-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0b4/11275169/5f707bd20cbd/biomolecules-14-00852-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0b4/11275169/668f858b9b01/biomolecules-14-00852-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0b4/11275169/d4f6a970f2b2/biomolecules-14-00852-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0b4/11275169/413d33d91d0e/biomolecules-14-00852-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0b4/11275169/264165b87c84/biomolecules-14-00852-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0b4/11275169/30eb204448cd/biomolecules-14-00852-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0b4/11275169/a17befc74b8c/biomolecules-14-00852-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0b4/11275169/259fa42b6b62/biomolecules-14-00852-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0b4/11275169/1c97c94f955e/biomolecules-14-00852-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0b4/11275169/9acbd167a54d/biomolecules-14-00852-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0b4/11275169/5f707bd20cbd/biomolecules-14-00852-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0b4/11275169/668f858b9b01/biomolecules-14-00852-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0b4/11275169/d4f6a970f2b2/biomolecules-14-00852-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0b4/11275169/413d33d91d0e/biomolecules-14-00852-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0b4/11275169/264165b87c84/biomolecules-14-00852-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0b4/11275169/30eb204448cd/biomolecules-14-00852-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0b4/11275169/a17befc74b8c/biomolecules-14-00852-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0b4/11275169/259fa42b6b62/biomolecules-14-00852-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0b4/11275169/1c97c94f955e/biomolecules-14-00852-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0b4/11275169/9acbd167a54d/biomolecules-14-00852-g010.jpg

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Potential applications of mesenchymal stem cells and their derived exosomes in regenerative medicine.间充质干细胞及其衍生的外泌体在再生医学中的潜在应用。
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