PPARβ/δ directs the therapeutic potential of mesenchymal stem cells in arthritis

Objectives To define how peroxisome proliferator-activated receptor (PPAR) β/δ expression level in mesenchymal stem cells (MSCs) could predict and direct both their immunosuppressive and therapeutic properties. PPARβ/δ interacts with factors such as nuclear factor-kappa B (NF-κB) and regulates the expression of molecules including vascular cell adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1. Since these molecules are critical for MSC function, we investigated the role of PPARβ/δ on MSC immunosuppressive properties. Methods We either treated human MSCs (hMSCs) with the irreversible PPARβ/δ antagonist (GSK3787) or derived MSCs from mice deficient for PPARβ/δ (PPARβ/δ−/− MSCs). We used the collagen-induced arthritis (CIA) as model of immune-mediated disorder and the MSC-immune cell coculture assays. Results Modulation of PPARβ/δ expression in hMSCs either using GSK3787 or hMSCs from different origin reveals that MSC immunosuppressive potential is inversely correlated with Ppard expression. This was consistent with the higher capacity of PPARβ/δ−/− MSCs to inhibit both the proliferation of T lymphocytes, in vitro, and arthritic development and progression in CIA compared with PPARβ/δ+/+ MSCs. When primed with proinflammatory cytokines to exhibit an immunoregulatory phenotype, PPARβ/δ−/− MSCs expressed a higher level of mediators of MSC immunosuppression including VCAM-1, ICAM-1 and nitric oxide (NO) than PPARβ/δ+/+ MSCs. The enhanced NO2 production by PPARβ/δ−/− MSCs was due to the increased retention of NF-κB p65 subunit on the κB elements of the inducible nitric oxide synthase promoter resulting from PPARβ/δ silencing. Conclusions Our study is the first to show that the inhibition or knockdown of PPARβ/δ in MSCs primes their immunoregulatory functions. Thus, the regulation of PPARβ/δ expression provides a new strategy to generate therapeutic MSCs with a stable regulatory phenotype

La qualité de vie en maison de repos :une recherche-action-participative

info:eu-repo/semantics/nonPublishe

Educational value of surgical videos on transabdominal pre-peritoneal hernia repair (TAPP) on YouTube

Purpose Transabdominal pre-peritoneal hernia repair (TAPP) is a worldwide performed surgery. Surgical videos about TAPP uploaded on the web, with YouTube being the most frequently used platform, may have an educational purpose, which, however, remains unexplored. This study aims to evaluate the 20 most viewed YouTube videos on TAPP through the examination of four experienced surgeons and assess their conformity to the guidelines on how to report laparoscopic surgery videos. Methods On April 1st 2019, we searched for the 20 most viewed videos on TAPP on YouTube. Selected videos were evaluated on their overall utility and quality according to the Global Operative Assessment of Laparoscopic Skills-Groin Hernia (GOALS-GH) and the Laparoscopic surgery Video Educational Guidelines (LAP-VEGaS). Results Image quality was poor for 13 videos (65%), good for 6 (30%) and in high definition for 1 (5%). Audio and written commentary were present in 55% of cases, while no video presented a detailed preoperative case description. Only 35% of the videos had a GOALS-GH score > 15, indicating good laparoscopic skills. Overall video conformity to the LAP-VEGaS guidelines was weak, with a median value of 12.5% (5.4-18.9%). Concordance between the examiners was acceptable for both the overall video quality (Cronbach's Alpha 0.685) and utility (0.732). Conclusions The most viewed TAPP videos available on YouTube in 2019 are not conformed to the LAP-VEGaS guidelines. Their quality and utility as a surgical learning tool are questionable. It is of upmost importance to improve the overall quality of free-access surgical videos due to their potential educational value