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

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 associated with the 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.