P-076 The Combination of Mesenchymal Stromal Cells and Infliximab Increases the Anti-Inflammatory Effect of the Treatment of Ulcerative Colitis

Crohn's disease (CD) is a chronic, recurring disease of the gastrointestinal tract of unclear etiology. One of the new approaches to CD therapy is the use of the possibilities of stem cells, in particular, mesenchymal stromal cells (MSCs). Currently, the use of MSC in clinical practice for the treatment of chronic inflammatory and autoimmune diseases is being studied in patients who receive concomitant therapy with other immunomodulatory medications. Aim. To evaluate the effectiveness of MSCs therapy in patients with CD receiving azathioprine (AZA). Materials and methods. The study included 34 patients with inflammatory (luminal) form of CD. The 1st group of patients (n=15) received anti-inflammatory therapy using MSCs culture in combination with AZA. The 2nd group (n=19) received MSCs without AZA. The severity of the attack was assessed in points in accordance with the of Crohn's disease activity index (CDAI). Immunoglobulins (IgA, IgG, IgM), interleukins (IL) 1β, 4, 10, tumor necrosis factor-α (TNF-α), interferon-γ (INF-γ), transforming growth factor-1β (TGF-1β), C-reactive protein (CRP), platelets and erythrocyte sedimentation rate (ESR) at 2, 6 and 12 months from the beginning of MSCs therapy. Results. The initial mean CDAI in the 1st group was 337.6±17.1 points, in the 2nd group - 332.7±11.0 points (p=0.3). In both groups of patients there was a significant decrease in CDAI after 2 months. From the beginning of therapy MSCs: in the 1st group to 118.9±12.4 points, in the 2nd - 120.3±14.1 points (p=0.7), after 6 months - 110.3±11.1 and 114.3±11.8 points (p=0.8), respectively. After 12 months CDAI in the 1st group was 99.9±10.8 points, in the 2nd group it was 100.6±12.1 points (p=0.8). The level of IgA, IgG, IgM was significantly lower in the group of patients with a longer history of the disease and long-term ASA. After the introduction of MSC in both groups of patients with BC, there was a tendency for the growth of pro - and anti-inflammatory cytokines, with a significantly lower level of pro-inflammatory cytokines - INF-γ, TNF-α, IL-1β - in the 1st group, indicating potentiation of the immunosuppressive effect of MSCs and AZA, which provides a more pronounced anti-inflammatory effect. Conclusion. Transplantation of MSCs promotes an increase in the serum of patients with CD initially reduced concentration of IG, cytokines and restoring their balance as the onset of clinical remission. The combination with AZA has a more pronounced anti-inflammatory effect.

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Human mesenchymal stromal cells broadly modulate high glucose-induced inflammatory responses of renal proximal tubular cell monolayers

Stem Cell Research & Therapy ◽

10.1186/s13287-019-1424-5 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 1

Author(s):

Md Nahidul Islam ◽

Tomás P. Griffin ◽

Elizabeth Sander ◽

Stephanie Rocks ◽

Junaid Qazi ◽

...

Keyword(s):

Rna Sequencing ◽

Mesenchymal Stromal Cells ◽

Inflammatory Mediators ◽

Stromal Cells ◽

High Glucose ◽

Cell Monolayers ◽

Proximal Tubular ◽

Anti Inflammatory ◽

Renal Proximal Tubular ◽

Inflammatory Effect

Abstract Background Renal proximal tubular epithelial cells (RPTEC) are dysfunctional in diabetic kidney disease (DKD). Mesenchymal stromal cells (MSC) may modulate DKD pathogenesis through anti-inflammatory mediators. This study aimed to investigate the pro-inflammatory effect of extended exposure to high glucose (HG) concentration on stable RPTEC monolayers and the influence of MSC on this response. Methods Morphologically stable human RPTEC/TERT1 cell monolayers were exposed to 5 mM and 30 mM (HG) D-glucose or to 5 mM D-glucose + 25 mM D-mannitol (MAN) for 5 days with sequential immunoassays of supernatants and end-point transcriptomic analysis by RNA sequencing. Under the same conditions, MSC-conditioned media (MSC-CM) or MSC-containing transwells were added for days 4–5. Effects of CM from HG- and MAN-exposed RPTEC/MSC co-cultures on cytokine secretion by monocyte-derived macrophages were determined. Results After 72–80 h, HG resulted in increased RPTEC/TERT1 release of interleukin (IL)-6, IL-8, monocyte chemoattractant protein (MCP)-1 and neutrophil gelatinase-associated lipocalin (NGAL). The HG pro-inflammatory effect was attenuated by concentrated (10×) MSC-CM and, to a greater extent, by MSC transwell co-culture. Bioinformatics analysis of RNA sequencing data confirmed a predominant effect of HG on inflammation-related mediators and biological processes/KEGG pathways in RPTEC/TERT1 stable monolayers as well as the non-contact-dependent anti-inflammatory effect of MSC. Finally, CM from HG-exposed RPTEC/MSC transwell co-cultures was associated with attenuated secretion of inflammatory mediators by macrophages compared to CM from HG-stimulated RPTEC alone. Conclusions Stable RPTEC monolayers demonstrate delayed pro-inflammatory response to HG that is attenuated by close proximity to human MSC. In DKD, this MSC effect has potential to modulate hyperglycemia-associated RPTEC/macrophage cross-talk.

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Effect of a Milk-Based Fruit Beverage Enriched with Plant Sterols and/or Galactooligosaccharides in a Murine Chronic Colitis Model

Foods ◽

10.3390/foods8040114 ◽

2019 ◽

Vol 8 (4) ◽

pp. 114 ◽

Cited By ~ 2

Author(s):

Gabriel López-García ◽

Antonio Cilla ◽

Reyes Barberá ◽

Amparo Alegría ◽

María Recio

Keyword(s):

Ulcerative Colitis ◽

Experimental Colitis ◽

Plant Sterols ◽

Mice Model ◽

Colon Tissue ◽

Clinical Model ◽

Need To Evaluate ◽

Anti Inflammatory ◽

Enriched Milk ◽

Inflammatory Effect

The potential anti-inflammatory effect of plant sterols (PS) enriched milk-based fruit beverages (PS, 1 g/100 mL) (MfB) with/without galactooligosaccharides (GOS, 2 g/100 mL) (MfB-G) in an experimental mice model of chronic ulcerative colitis was evaluated. Beverages were orally administered to mice every day by gavage to achieve PS and GOS doses of 35 and 90 mg/kg, respectively, and experimental colitis was induced by giving mice drinking water ad libitum containing 2% (w/v) dextran sulphate sodium (DSS) for 7 days, alternating with periods without DSS up to the end of the study (56 days). MfB beverage showed significant reduction of symptoms associated to ulcerative colitis and improved the colon shortening and mucosal colonic damage, but it was not able to reduce the increase of myeloperoxidase levels produced by DSS. MfB-G showed higher incidence of bloody feces and loss of stool consistency than MfB, as well as high levels of immune cells infiltration in colon tissue and myeloperoxidase. Therefore, PS-enriched milk-based fruit beverage could be an interesting healthy food to extend the remission periods of the diseases and the need to evaluate, in a pre-clinical model, the anti-inflammatory effect of the combination of bioactive compounds in the context of a whole food matrix.

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