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.

Introduction

Coronavirus disease 2019 rapidly shifted health care toward telehealth. We assessed satisfaction with and preferences for telehealth among patients with irritable bowel syndrome (IBS).

Methods

We conducted a cross-sectional survey in an integrated healthcare system in Southern California with members aged 18-90 years with an International Classification of Diseases 9 and 10 codes for IBS from office-based encounters between June 1, 2018, and June 1, 2020. Eligible patients were emailed a survey assessing telehealth satisfaction overall and by patient-related factors, IBS characteristics, health and technologic literacy, utilization, and coronavirus disease 2019 perceptions. We identified perceived telehealth benefits and challenges. Multivariable logistic regression identified predictors of telehealth dissatisfaction.

Results

Of 44,789 surveys sent, 5,832 (13.0%) patients responded and 1,632 (3.6%) had Rome IV IBS. Among 1,314 (22.5%) patients with IBS and prior telehealth use (mean age 52.6 years [17.4]; 84.9% female; and 59.4% non-Hispanic White, 29.0% Hispanic, and 5.6% non-Hispanic Black), 898 (68.3%) were satisfied, 130 (9.9%) were dissatisfied, and 286 (21.8%) felt neutral. In addition, 78.6% would use telehealth again. Independent predictors of telehealth dissatisfaction include social media use of once a week or less (adjusted odds ratio [OR] = 2.1; 1.3-3.5), duration of IBS for <1 year (adjusted OR = 8.2; 1.9-35.8), and willingness to travel 60 plus minutes for face-to-face visits (adjusted OR = 2.6; 1.4-3.7). Patients' main concern with telehealth was a lack of physical examination.

Discussion

Most of the patients with IBS are satisfied with telehealth. Shorter duration of IBS diagnosis, comfort with technology, and increased willingness to travel were associated with telehealth dissatisfaction. These predictors may help identify a target population for a focused IBS-telehealth program.

The ability of mesenchymal stromal cells (MSCs) to suppress immune responses combined with their potential to actively participate in tissue repair provides a strong rationale for the use of MSCs as a new treatment option in diseases characterized by inflammation and severe tissue damage, such as Crohn's disease (CD) and perianal fistulas. Multiple studies have shown that MSCs suppress a range of immune cells, such as dendritic cells (DC), naïve and effector T cells, and natural killer (NK) cells. Recently published papers attribute the immunosuppressive capacity of MSCs to soluble factors produced by MSCs, such as prostaglandin E2 (PGE(2)), inducible nitric oxide synthase (iNOS), and indoleamine 2,3-dioxygenase (IDO). Promising results are obtained from phase I and II clinical trials with autologous and allogeneic MSCs as treatment for refractory CD and perianal fistulas; however the question remains: what are the molecular mechanisms underlying the immunomodulating properties of MSCs? This paper highlights the present knowledge on the immunosuppressive effects of MSCs and its complexity in relation to CD and perianal fistulas.

Objective

Inflammatory Bowel Disease (IBD) is an inflammatory disorder of the gastrointestinal tract that can necessitate hospitalization and the use of expensive biologics. Models predicting these interventions may improve patient quality of life and reduce expenditures.

Materials and methods

We used insurance claims from 2011 to 2013 to predict IBD-related hospitalizations and the initiation of biologics. We derived and optimized our model from a 2011 training set of 7771 members, predicting their outcomes the following year. The best-performing model was then applied to a 2012 validation set of 7450 members to predict their outcomes in 2013.

Results

Our models predicted both IBD-related hospitalizations and the initiation of biologics, with average positive predictive values of 17% and 11%, respectively - each a 200% improvement over chance. Further, when we used topic modeling to identify four member subpopulations, the positive predictive value of predicting hospitalization increased to 20%.

Discussion

We show that our hospitalization model, in concert with a mildly-effective interventional treatment plan for members identified as high-risk, may both improve patient outcomes and reduce insurance expenditures.

Conclusion

The success of our approach provides a roadmap for how claims data can complement traditional medical decision making with personalized, data-driven predictive medicine.

Background & aims

Persistent activation of the inflammatory response contributes to the development of inflammatory bowel diseases, which increase the risk of colorectal cancer. We aimed to identify microRNAs that regulate inflammation during the development of ulcerative colitis (UC) and progression to colitis-associated colon cancer (CAC).

Methods

We performed a quantitative polymerase chain reaction 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 also were given an inhibitor of microRNA214 (miR214).

Results

A high-throughput functional screen of the human microRNAome found that miR214 regulated the activity of nuclear factor-κB. Higher levels of miR214 were detected in colon tissues from patients with active UC or CAC than from patients with other disorders or controls and correlated with disease progression. Bioinformatic and genome-wide profile analyses showed 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 signal transducer and activator of transcription 3 (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 biopsy specimens from patients with active UC, the miR214 inhibitor reduced inflammation by increasing levels of PDLIM2 and PTEN.

Conclusions

Interleukin-6 up-regulates STAT3-mediated transcription of miR214 in colon tissues, which reduces levels of PDLIM2 and PTEN, increases phosphorylation of AKT, and activates nuclear factor-κB. The activity of this circuit correlates with disease activity in patients with UC and progression to colorectal cancer.