Immunomodulatory effect of different stimuli in mesenchymal stem cells

• Autor(a) principal: Gonçalves, Diana Rafaela Costa
• Data de Publicação: 2022
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10773/38113
• topic: Mesenchymal stem cells; Biophysical cues; Mechanosensing; Biochemical cues; Priming; Cellular behaviour

Modulating stem cells activity towards specific responses is one of the major challenges in tissue regeneration field. The conventional function of mesenchymal stem cells (MSCs) relies on distinct interactions that are regulated by the microenvironment. MSCs can sense inflammation and exert an anti-inflammatory activity through secretion of bioactive factors (secretome). This secretome immunomodulatory capacity tends to be improved after stimulation with pro-inflammatory cytokines. Here, the effects of various time-dependent regimens were investigated, including the unprecedently pulsatile delivery of IFN-γ to human MSCs derived from adipose tissue (hASCs). To meet the need for high MSCs fixation in defect sites, cell culture was carried out in three-dimensional (3D) alginate hydrogels. The 3D encapsulation of hASCs resulted in the production of a less anti-inflammatory profile (decreasing IL-10 secretion) upon exposure to IFN-γ than in cytokine-free samples. M1 macrophages exhibited a pro-inflammatory phenotype after being stimulated by MSCs in a pulsatile manner. With the exception of FGF-basic and G-CSF, the secretion of growth factors was generally not significantly changed by the exposure to IFN-γ. The unexpected composition of MSCs' secretome in response to cytokine stimulation highlight the necessity of thoroughly examining MSCs' behaviour in various engineered and physiologically realistic setups, abandoning pre-existing ideas.