The immunomodulatory effects of adipose‐derived mesenchymal stem cells and mesenchymal stem cells‐conditioned medium in chronic colitis

Abstract

Inflammatory bowel disease (IBD) as a chronic recurrent disorder is characterized by mucosal immune response dysregulation, which is more prevalent in the youth. Adipose-derived mesenchymal stem cells (ADMSCs) are the multipotent cells that can be effective in immune response regulation via cell-cell interaction and their secretions. In this study, the effects of ADMSCs and mesenchymal stem cell-conditioned medium (MSC-CM) were evaluated on dextran sulfate sodium (DSS)-induced colitis in mice. Chronic colitis was induced in female C57BL/6 mice using 2% DSS in drinking water for three cycles; there were 4 days of DSS-water administration that was followed by 7 days of DSS-free water, in a cycle. ADMSCs, 10 cells per mouse, were injected intraperitoneally (IP), whereas the MSC-CM injection was also performed six times from the last day of DSS in Cycle 1. Clinical symptoms were recorded daily. The colon pathological changes, cytokine levels, and regulatory T (Treg) cell percentages were then analyzed. After receiving ADMSCs and MSC-CM in colitis mice, the clinical symptoms and disease activity index were improved and the survival rate was increased. The histopathological examination also showed tissue healing in comparison with the nontreated group. In addition, the increased level of transforming growth factor beta, increased percentage of Treg cells, increased level of interleukin (IL)-10, and decreased level of IL-17 were observed after the treatment. This study showed the regulatory effects of ADMSCs and MSC-CM on inflammatory responses. Therefore, the use of ADMSCs and MSC-CM can be introduced as a new and effective therapeutic approach for patients with colitis.

Mesenchymal stem cell–derived conditioned medium attenuate angiotensin II‐induced aortic aneurysm growth by modulating macrophage polarization

“…Indeed, it has been demonstrated that the administration of MSCs-CM was as effective as MSC treatment itself in various diseases. 14,15,17 Recently, MSCs have been shown to prevent AA formation and progression in a variety of AA models. [10][11][12]25 In the present study, we investigated the effects and Macrophages are essential mediators of the inflammatory response and play an important role in inflammation-associated diseases.…”

“…BM‐MSC‐derived conditioned medium (MSCs‐CM) is thought to be a potent secretory component of BM‐MSCs containing specific cytokines, growth factors and small RNAs, which play an important role in MSC‐mediated therapeutic effects . Several recent studies have demonstrated that administration of MSCs‐CM was as effective as BM‐MSCs treatment itself in animal models of tissue injury and inflammatory diseases . Recent studies have disclosed that BM‐MSCs reduced inflammatory response and promoted tissue repair by inducing macrophage phenotype conversion from M1 to M2 in various disease models .…”

“…13 Several recent studies have demonstrated that administration of MSCs-CM was as effective as BM-MSCs treatment itself in animal models of tissue injury and inflammatory diseases. [14][15][16][17] Recent studies have disclosed that BM-MSCs reduced inflammatory response and promoted tissue repair by inducing macrophage phenotype conversion from M1 to M2 in various disease models. [18][19][20][21][22] Previously, Hashizume and colleagues have reported that BM-MSCs attenuated AngII-induced AA growth in apoE −/− mice by surgically implanting BM-MSCs sheet on the surface of aortic adventitial.…”

Effect of Hypoxia Preconditioned Adipose-Derived Mesenchymal Stem Cell Conditioned Medium on Cerulein-Induced Acute Pancreatitis in Mice

“…2,9,14,15 Mesenchymal stem cells (MSCs) and their secreted molecules-which possess regenerative, anti-inflammatory and antioxidative properties-have been suggested as a potential therapeutic approach in many inflammatory and immune-mediated disorders. [16][17][18][19][20][21][22] Jung et al, for the first time in 2011, reported the protective effects of MSCs in treating AP. 23 Subsequently, several studies demonstrated that MSC therapy can decrease inflammatory mediators and mitigate histopathological changes in pancreatitis through direct differentiation to acinar cells or indirect immunomodulatory effects.…”

“…20,27,28 Recent studies reported the protective effects of MSC-derived conditioned medium (MSC-CM) or MSC-derived extracellular vesicles (MSC-EVs) in some animal models of diseases. 17,20,22,27,29,30 Proteomics analysis of MSC-CM has identified more than 100 proteins (including cytokines, chemokines and growth factors) with anti-inflammatory, anti-apoptotic, anti-fibrotic and regenerative effects. 28,31 It has been shown that exposure of MSCs to hypoxic conditions might enhance their immunomodulatory and regenerative properties via over-expression of cytoprotective genes and secretory factors.…”