Mesenchymal stem cell-conditioned medium reduces disease severity and immune responses in inflammatory arthritis

We evaluated the therapeutic potential of mesenchymal stem cell-conditioned medium (CM-MSC) as an alternative to cell therapy in an antigen-induced model of arthritis (AIA). Disease severity and cartilage loss were evaluated by histopathological analysis of arthritic knee joints and immunostaining of aggrecan neoepitopes. Cell proliferation was assessed for activated and naïve CD4+ T cells from healthy mice following culture with CM-MSC or co-culture with MSCs. T cell polarization was analysed in CD4+ T cells isolated from spleens and lymph nodes of arthritic mice treated with CM-MSC or MSCs. CM-MSC treatment significantly reduced knee-joint swelling, histopathological signs of AIA, cartilage loss and suppressed TNFα induction. Proliferation of CD4+ cells from spleens of healthy mice was not affected by CM-MSC but reduced when cells were co-cultured with MSCs. In the presence of CM-MSC or MSCs, increases in IL-10 concentration were observed in culture medium. Finally, CD4+ T cells from arthritic mice treated with CM-MSC showed increases in FOXP3 and IL-4 expression and positively affected the Treg:Th17 balance in the tissue. CM-MSC treatment reduces cartilage damage and suppresses immune responses by reducing aggrecan cleavage, enhancing Treg function and adjusting the Treg:Th17 ratio. CM-MSC may provide an effective cell-free therapy for inflammatory arthritis

Effect of time to surgery in resectable pancreatic cancer: a systematic review and meta-analysis.

PURPOSE Achieving surgical resection is essential if patients with pancreatic ductal adenocarcinoma (PDAC) have a chance for cure. The objective of this study was to evaluate the effect of time to surgery on resection rates in patients with resectable PDAC. METHODS A systematic literature search was performed to identify studies reporting times to surgery and resection rates. Meta-regression models were then produced to assess the relationship between time to surgery and resection rates, using both intra- and inter-study comparisons. RESULTS A total of 21 studies were included, comprising n = 2171 patients, with a pooled resection rate of 76%. Intra-study meta-analysis of the five studies that reported comparisons between patients with vs. without preoperative biliary drainage (PBD) or with long vs. short delays to surgery found earlier surgery to be associated with a significantly higher rate of resection (pooled odds ratio 1.93, 95% CI: 1.25-2.97, P = 0.003). Inter-study meta-regression across all studies found a tendency for resection rates to decline with increasing time from CT or ERCP to surgery (gradient - 0.13 log-odds per week, 95% CI - 0.28, 0.03, P = 0.100), although this did not reach statistical significance, in part due to considerable heterogeneity between studies. CONCLUSION Pathways to reduce the time to surgery, primarily by avoiding PBD, demonstrate significantly greater resection rates. Early surgery, including avoidance of PBD, not only provides patients with the benefit of avoiding harm associated with PBD but also with a greater chance of undergoing resection