RESUMO
There is an active search for the ideal strategy to potentialize the effects of Mesenchymal Stem-Cells (MSCs) over the immune system. Also, part of the scientific community is seeking to elucidate the therapeutic potential of MSCs secretome and its extracellular vesicles (EVs), in order to avoid the complexity of a cellular therapy. Here, we investigate the effects of human adipose MSCs (AMSCs) licensing with INF-γ and TLR3 agonist over AMSCs proliferation, migration, as well as the immunomodulatory function. Furthermore, we evaluated how the licensing of AMSCs affected the immunomodulatory function of AMSC derived-secretome, including their EVs. INF-γ licensed-AMSCs presented an elevated expression of indoleamine 2,3-dioxygenase (IDO), accompanied by increased ICAM-1, as well as a higher immunosuppressive potential, compared to unlicensed AMSCs. Interestingly, the conditioned medium obtained from INF-γ licensed-AMSCs also revealed a slightly superior immunosuppressive potential, compared to other licensing strategies. Therefore, unlicensed and INF-γ licensed-AMSCs groups were used to isolate EVs. Interestingly, EVs isolated from both groups displayed similar capacity to inhibit T-cell proliferation. EVs isolated from both groups shared similar TGF-ß and Galectin-1 mRNA content but only EVs derived from INF-γ licensed-AMSCs expressed IDO mRNA. In summary, we demonstrated that INF-γ licensing of AMSCs provides an immunosuppressive advantage both from a cell-cell contact-dependent perspective, as well as in a cell-free context. Interestingly, EVs derived from unlicensed and INF-γ licensed-AMSCs have similar ability to control activated T-cell proliferation. These results contribute towards the development of new strategies to control the immune response based on AMSCs or their derived products.
Assuntos
Vesículas Extracelulares/imunologia , Vesículas Extracelulares/metabolismo , Tolerância Imunológica , Interferon gama/imunologia , Células-Tronco Mesenquimais/imunologia , Células-Tronco Mesenquimais/metabolismo , Tecido Adiposo/citologia , Movimento Celular , Proliferação de Células , Sobrevivência Celular , Células Cultivadas , Galectina 1/metabolismo , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Células-Tronco Mesenquimais/citologia , Receptor 3 Toll-Like/antagonistas & inibidores , Fator de Crescimento Transformador beta/metabolismoRESUMO
AIM: We reviewed clinical trials addressing the effect of glucacon-like peptide 1 (GLP-1) or GLP-1 receptor agonists (GLP-1RA) on energy expenditure (EE) in adults. MATERIALS AND METHODS: PubMed, Science Direct and Web of Science were searched for clinical trials investigating the effect of GLP-1 or GLP-1RA on EE in adults. RESULTS: Ten trials (93 participants) assessed the effect of GLP-1 administration over 1 to 48â¯h and found no change in resting EE (REE). Two out of three trials (62 participants) reported a significant decrease in diet-induced thermogenesis (DIT) following GLP-1 administration. Ten trials with exenatide (10⯵g bid, for 10-52â¯weeks) or liraglutide (0.6, 1.2, 1.8 or 3â¯mg, for 3â¯days-52â¯weeks), with a total of 282 participants, indicated a neutral effect of these GLP-1RA on REE, DIT or physical activity-induced EE. Importantly, the longest trial with GLP-1RA reported a significant increase in REE in response to treatment with both exenatide or liraglutide and most trials reported that GLP-1RA-induced weight loss was not accompanied by decreased REE. CONCLUSIONS: This review indicates that GLP-1 has no short-term effect on REE but may decrease DIT. The GLP-1RA exenatide and liraglutide have a neutral effect on REE, although it is not possible to rule out an increase in REE following prolonged treatment.