Due to their immunosuppressive properties, mesenchymal stem cells (MSC) have been evaluated for the treatment of immunological diseases. However, the animal-derived growth supplements utilized for MSC manufacturing may lead to clinical complications. Characterization of alternative media formulations is imperative for MSC therapeutic application. Human BMMSC and AdMSC were expanded in media supplemented with either human platelet lysates (HPL), serum-free media/xeno-free FDA-approved culture medium (SFM/XF), or fetal bovine serum (FBS) and the effects on their properties were investigated. The immunophenotype of resting and IFN-γ primed BMMSC and AdMSC remained unaltered in all media. Both HPL and SFM/XF increased the proliferation of BMMSC and AdMSC. Expansion of BMMSC and AdMSC in HPL increased their differentiation, compared to SFM/XF and FBS. Resting BMMSC and AdMSC, expanded in FBS or SFM/XF, demonstrated potent immunosuppressive properties in both non-primed and IFN-γ primed conditions, whereas HPL-expanded MSC exhibited diminished immunosuppressive properties. Finally, IFN-γ primed BMMSC and AdMSC expanded in SFM/XF and HPL expressed attenuated levels of IDO-1 compared to FBS. Herein, we provide strong evidence supporting the use of the FDA-approved SFM/XF medium, in contrast to the HPL medium, for the expansion of MSC towards therapeutic applications.
A Standard Set of outcome measures for IBD has been developed based on evidence, patient input and specialist consensus. It provides an international template for meaningful, comparable and easy-to-interpret measures as a step towards achieving value-based healthcare in IBD.
Background & Aims
Persistent activation of the inflammatory response contributes to development of inflammatory bowel diseases, which increase the risk of colorectal cancer. We aimed to identify microRNAs that regulate inflammation during development of ulcerative colitis (UC) and progression to colitis-associated colon cancer (CAC).
Methods
We performed quantititave PCR analysis to measure microRNAs in 401 colon specimens from patients with UC, Crohn's disease, irritable bowel syndrome, sporadic colorectal cancer, or CAC, as well as subjects without these disorders (controls); levels were correlated with clinical features and disease activity of patients. Colitis was induced in mice by administration of dextran sodium sulfate (DSS), and carcinogenesis was induced by addition of azoxymethane; some mice were also given inhibitor of microRNA214 (miR214).
Results
A high-throughput functional screen of the human microRNAome found that miR214 regulated the activity of nuclear factor κB (NFκB). Higher levels of miR214 were detected in colon tissues from patients with active UC or CAC than patients with other disorders or controls and correlated with disease progression. Bioinformatic and genome-wide profile analyses revealed that miR214 activates an inflammatory response and is amplified through a feedback loop circuit mediated by phosphatase and tensin homolog (PTEN) and PDZ and LIM domain 2 (PDLIM2). Interleukin-6 induced STAT3-mediated transcription of miR214. A miR214 chemical inhibitor blocked this circuit and reduced the severity of DSS-induced colitis in mice, as well as the number and size of tumors that formed in mice given azoxymethane and DSS. In fresh colonic biopsies from patients with active UC, the miR214 inhibitor reduced inflammation by increasing levels of PDLIM2 and PTEN.
Conclusions
Interleukin-6 upregulates STAT3-mediated transcription of miR214 in colon tissues, which reduces levels of PDLIM2 and PTEN, increases phosphorylation of AKT, and activates NFκB. The activity of this circuit correlates with disease activity in patients with UC and progression to colorectal cancer.
We developed and validated a scoring system to monitor disease activity in patients with CD and UC that can be used with mobile technologies. The indices identified clinical disease activity with area under the receiver operating characteristic curve values of 0.9 or higher in patients with CD or UC, and endoscopic activity in patients with UC but not CD.
Background and objectives
Value-based healthcare (VBHC) is considered to be the solution that will improve quality and decrease costs in healthcare. Many hospitals are implementing programs on the basis of this strategy, but rigorous scientific reports are still lacking. In this pilot study, we present the first-year outcomes of a VBHC program for inflammatory bowel disease (IBD) management that focuses on highly coordinated care, task differentiation of providers, and continuous home monitoring.
Methods
IBD patients treated within the VBHC program were identified in an administrative claims database from a commercial insurer allowing comparisons to matched controls. Only patients for whom data were available the year before and after starting the program were included. Healthcare utilization including visits, hospitalizations, laboratory and imaging tests, and medications were compared between groups.
Results
In total, 60 IBD patients treated at the VBHC Center were identified and were matched to 177 controls. Significantly fewer upper endoscopies were performed (−10%, P=0.012), and numerically fewer surgeries (−25%, P=0.49), hospitalizations (−28%, 0=0.71), emergency department visits (-37%, P=0.44), and imaging studies (−25 to −86%) were observed. In addition, 65% fewer patients (P=0.16) used steroids long term. IBD-related costs were 16% ($771) lower than expected (P=0.24).
Conclusion
These are the first results of a successfully implemented VBHC program for IBD. Encouraging trends toward fewer emergency department visits, hospitalizations, and long-term corticosteroid use were observed. These results will need to be confirmed in a larger sample with more follow-up.
This analysis shows 2010-2012 utilization and medication patterns of IBD health care in the United States and suggests that improvement can be obtained through enhanced guidelines adherence.
Patients with IBD in clinical remission still cope with significantly more presenteeism and work limitations than controls; this translates in higher indirect costs and decreased quality of life. The majority have not made any adjustments to battle these problems.
Both MSC and HSC therapy offer clinical potential, but currently are not routinely used for IBD treatment. MSC therapy seems well tolerated but results on efficacy are conflicting. HSC transplantation is shown to be effective but safety concerns remain. Nonetheless, for severe refractory IBD cases, stem cell therapy could well become the next-generation treatment option.
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