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Thymocyte viability after co-culture with thymic stromal cells. (A) Gate strategy of FSCxSSC dotplot and CD4/CD8 subsets of thymocytes. Dead and viable cells were determined by propidium iodide staining. (B) Inside gate of viable thymocytes, the percentual of thymocytes was showed in three conditions: alone (3.85%), tran-
Source publication
Insulin-like growth factor-1 (IGF-1), in addition to its classic effects on cell proliferation and organism growth, has pleiotropic actions on the immune system, particularly on the thymus. Thus, the objective of this study was to evaluate the influence of IGF-1 on molecules involved in the survival of thymocytes in vitro using a co-culture system...
Contexts in source publication
Context 1
... A co-culture system permits these interactions needed for thymocytes to remain stimulated and functional (Young and Angel 2006). Thus, thymic stromal cells and thymocytes were co-cultured for 72 h and treated daily with IGF-1. At the end of the treatment, thymocyte viability was evaluated using Annexin-V and propidium iodide (PI) staining ( Fig. 2A). Also, there were groups of thymocytes cultured alone in the culture dish (in the absence of stromal cells), and groups of thymocytes cultured into transwell inserts, but still receiving soluble signals from the stromal cells (there was no direct contact with the stromal cells). As a result, it was observed that alone or ...
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... transwell inserts, but still receiving soluble signals from the stromal cells (there was no direct contact with the stromal cells). As a result, it was observed that alone or transwell-cultivated thymocytes had a lower viability after 72 h in culture; however, when these cells have direct contact with stromal cells, this viability was triplicated (Fig. ...
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... called viable cells, while 10.7% were only positive for Annexin-V (early apoptosis) and 5.09% were double-positive for the markers (late apoptosis). In the co-cultures treated with IGF-1, the percentage of cell viability and early and late apoptosis remained similar to the control group (72.2%, 12.5%, and 5.08%, respectively), as demonstrated in Fig. 2C, ...
Citations
Growth hormone (GH) is a classic pituitary-derived hormone crucial to body growth and metabolism. In the pituitary gland, GH production is stimulated by GH-releasing hormone and inhibited by somatostatin. GH secretion can also be induced by other peptides, such as ghrelin, which interacts with receptors present in somatotropic cells. It is well established that GH acts directly on target cells or indirectly by stimulating the production of insulin-like growth factors (IGFs), particularly IGF-1. Notably, such somatotropic circuitry is also involved in the development and function of immune cells and organs, including the thymus. Interestingly, GH, IGF-1, ghrelin, and somatostatin are expressed in the thymus in the lymphoid and microenvironmental compartments, where they stimulate the secretion of soluble factors and extracellular matrix molecules involved in the general process of intrathymic T-cell development. Clinical trials in which GH was used to treat immunocompromised patients successfully recovered thymic function. Additionally, there is evidence that the reduction in the function of the somatotropic axis is associated with age-related thymus atrophy. Treatment with GH, IGF-1 or ghrelin can restore thymopoiesis of old animals, thus in keeping with a clinical study showing that treatment with GH, associated with metformin and dehydroepiandrosterone, could induce thymus regeneration in healthy aged individuals. In conclusion, the molecules of the somatotrophic axis can be envisioned as potential therapeutic targets for thymus regeneration in age-related or pathological thymus involution.
