Assessment of the Immunosuppressive Potential of INF-γ Licensed Adipose Mesenchymal Stem Cells, Their Secretome and Extracellular Vesicles.

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.

Assessment of maximal lactate steady state during treadmill exercise in SHR.

BACKGROUND: Spontaneously hypertensive rats (SHR) are one of the main animal models used for studying the effects of exercise on hypertension. Therefore, the determination of adequate intensity has been essential for secure and optimized exercise prescriptions concerning hypertensive subjects. This study aimed to identify the MLSS in SHR by using a treadmill test to improve the protocols and further prescriptions of exercise intensity. FINDINGS: In order to carry out this determination, SHR (n = 10) animals (~17.5 weeks; 227.4 ± 29.3 g; 172.4 ± 8.1 mmHg systolic blood pressure) were divided into two groups (G1 n = 5; G2 n = 5). Rats underwent a test with three different velocities to determine the MLSS. The MLSS was considered as the highest effort intensity where the blood lactate did not vary more than 1 mmol.L-1 from the 10th to the 25th minute. The MLSS was reached at a velocity of 20 m.min-1 with 3.8 ± 0.5 mmol.L-1 of lactate for G1. Additionally, the results were validated in G2. However, when the test was applied at 25 m.min-1, there was no stabilization of BLC in G1 and G2. CONCLUSIONS: In this study it was possible to identify the MLSS in SHR rats, which is an excellent evaluation tool to control exercise intensity. These data are of considerable importance in studies using physical exercise as a means of research in hypertension and may lead to the intensity of exercise being prescribed more appropriately.