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葡萄糖预处理人蜕膜下基质干细胞增加其移植和抗糖尿病特性。

Preconditioning of Human Decidua Basalis Mesenchymal Stem/Stromal Cells with Glucose Increased Their Engraftment and Anti-diabetic Properties.

机构信息

Stem Cells and Regenerative Medicine Department, King Abdullah International Medical Research Center, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Mail Code 1515, P.O. Box 22490, Riyadh, 11426, Kingdom of Saudi Arabia.

National Center for Stem Cell Technology, Life Sciences and Environment Research Institute, King Abdulaziz City for Science and Technology, P.O Box 6086, Riyadh, 11442, Kingdom of Saudi Arabia.

出版信息

Tissue Eng Regen Med. 2020 Apr;17(2):209-222. doi: 10.1007/s13770-020-00239-7. Epub 2020 Feb 19.

Abstract

BACKGROUND

Mesenchymal stem/stromal cells (MSCs) from the decidua basalis (DBMSCs) of the human placenta have important functions that make them potential candidates for cellular therapy. Previously, we showed that DBMSC functions do not change significantly in a high oxidative stress environment, which was induced by hydrogen peroxide (HO) and immune cells. Here, we studied the consequences of glucose, another oxidative stress inducer, on the phenotypic and functional changes in DBMSCs.

METHODS

DBMSCs were exposed to a high level of glucose, and its effect on DBMSC phenotypic and functional properties was determined. DBMSC expression of oxidative stress and immune molecules after exposure to glucose were also identified.

RESULTS

Conditioning of DBMSCs with glucose improved their adhesion and invasion. Glucose also increased DBMSC expression of genes with survival, proliferation, migration, invasion, anti-inflammatory, anti-chemoattractant and antimicrobial properties. In addition, DBMSC expression of B7H4, an inhibitor of T cell proliferation was also enhanced by glucose. Interestingly, glucose modulated DBMSC expression of genes involved in insulin secretion and prevention of diabetes.

CONCLUSION

These data show the potentially beneficial effects of glucose on DBMSC functions. Preconditioning of DBMSCs with glucose may therefore be a rational strategy for increasing their therapeutic potential by enhancing their engraftment efficiency. In addition, glucose may program DBMSCs into insulin producing cells with ability to counteract inflammation and infection associated with diabetes. However, future in vitro and in vivo studies are essential to investigate the findings of this study further.

摘要

背景

人胎盘底蜕膜间充质干细胞(DBMSCs)具有重要的功能,使其成为细胞治疗的潜在候选者。此前,我们发现 DBMSC 功能在由过氧化氢(HO)和免疫细胞诱导的高氧化应激环境中不会发生显著变化。在这里,我们研究了另一种氧化应激诱导剂葡萄糖对 DBMSCs 表型和功能变化的影响。

方法

将 DBMSCs 暴露于高浓度葡萄糖中,确定其对 DBMSC 表型和功能特性的影响。还鉴定了 DBMSC 在暴露于葡萄糖后氧化应激和免疫分子的表达。

结果

用葡萄糖对 DBMSCs 进行预处理可改善其黏附和侵袭能力。葡萄糖还增加了具有生存、增殖、迁移、侵袭、抗炎、抗趋化和抗菌特性的 DBMSC 基因的表达。此外,葡萄糖还增强了 B7H4 的表达,B7H4 是 T 细胞增殖的抑制剂。有趣的是,葡萄糖调节了与胰岛素分泌和预防糖尿病相关的 DBMSC 基因的表达。

结论

这些数据表明葡萄糖对 DBMSC 功能具有潜在的有益影响。因此,用葡萄糖对 DBMSCs 进行预处理可能是通过提高其植入效率来增强其治疗潜力的合理策略。此外,葡萄糖可能将 DBMSCs 编程为具有抵抗与糖尿病相关的炎症和感染能力的胰岛素产生细胞。然而,未来的体外和体内研究对于进一步研究本研究的结果至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f46/7105536/3e3d09981ac9/13770_2020_239_Fig1_HTML.jpg

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