The effect of conditioned medium from human amniotic membrane-derived mesenchymal stem cells on thymus involution

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences Pub Date : 2025-02-01 DOI:10.1016/j.lfs.2024.123366

Catarina S. Silva , Marta R. Casanova , Pedro Ferreirinha , Alain da Silva Morais , Hugo Osório , Ana C. Lima , Joana F. Fangueiro , Mariana T. Cerqueira , Rui L. Reis , Nuno L. Alves , Albino Martins , Nuno M. Neves

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引用次数: 0

Abstract

Aims

The development and selection of T cells occur within the thymus. This organ involutes throughout life, compromising the generation of T cells and, consequently, the efficacy of the immune system. Mesenchymal stem cells (MSC) have beneficial effects on the immune system. Therefore, MSC have been applied in different pathologies related with thymic function. However, there is a lack of knowledge on the potential role of MSC-derived secretome on thymus involution. This work aims at studying the effect of human amniotic membrane-derived MSC conditioned media (hAMMSC CM) on aged thymus.

Materials and methods

The proteomic profile of hAMMSC CM was determined by liquid chromatography-tandem mass spectrometry. The CM was then intravenously injected in 12 months old mice, and the thymic stromal compartment and the different T cell populations characterized by flow cytometry.

Key findings

The hAMMSC CM is mostly enriched in proteins involved in extracellular matrix interaction, composition and organization, endodermal cell differentiation and angiogenesis. Its intravenous administration tends to increase the total thymic cellularity. A positive effect on the thymic epithelial cell (TEC) compartment was observed, with an increase of all TEC subsets. The hAMMSC CM also induced an increase in the thymocyte populations, accompanied by a confirmed positive selection. Mature single positive thymocytes expressed high levels of CD62L and low levels of CD24, indicating their ability to egress the thymus into the periphery.

Significance

Experimental findings support the potential role of hAMMSC CM as a cell-free therapeutic strategy for thymus involution.

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人羊膜间充质干细胞条件培养基对胸腺复旧的影响。

目的：T细胞的发育和选择发生在胸腺内。这个器官在整个生命过程中都会衰竭，影响T细胞的产生，从而影响免疫系统的功效。间充质干细胞（MSC）对免疫系统有有益的作用。因此，MSC已被应用于与胸腺功能相关的不同病理。然而，关于骨髓间质干细胞衍生的分泌组在胸腺复旧中的潜在作用的知识缺乏。本研究旨在研究人羊膜源间充质干细胞条件培养基（hAMMSC CM）对老年胸腺的影响。材料与方法：采用液相色谱-串联质谱法测定hAMMSC CM的蛋白质组学特征。12月龄小鼠经静脉注射CM，胸腺间质室和不同的T细胞群通过流式细胞术表征。主要发现：hAMMSC CM主要富含参与细胞外基质相互作用、组成和组织、内胚层细胞分化和血管生成的蛋白质。静脉给药可增加胸腺总细胞数。观察到胸腺上皮细胞（TEC）室的积极作用，所有TEC亚群的增加。hAMMSC CM也诱导胸腺细胞数量增加，并伴有确认的阳性选择。成熟的单个阳性胸腺细胞表达高水平的CD62L和低水平的CD24，表明它们有能力进入胸腺外周。意义：实验结果支持hAMMSC CM作为胸腺退化的无细胞治疗策略的潜在作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Life sciences 医学-药学

CiteScore

12.20

自引率

1.60%

发文量

841

审稿时长

6 months

期刊介绍： Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed. The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.