Dataset Information

Neuroprotective Potential of Mesenchymal Stem Cell-Based Therapy in Acute Stages of TNBS-Induced Colitis in Guinea-Pigs.

ABSTRACT:

Background & aims

The therapeutic benefits of mesenchymal stem cells (MSCs), such as homing ability, multipotent differentiation capacity and secretion of soluble bioactive factors which exert neuroprotective, anti-inflammatory and immunomodulatory properties, have been attributed to attenuation of autoimmune, inflammatory and neurodegenerative disorders. In this study, we aimed to determine the earliest time point at which locally administered MSC-based therapies avert enteric neuronal loss and damage associated with intestinal inflammation in the guinea-pig model of colitis.

Methods

At 3 hours after induction of colitis by 2,4,6-trinitrobenzene-sulfonate (TNBS), guinea-pigs received either human bone marrow-derived MSCs, conditioned medium (CM), or unconditioned medium by enema into the colon. Colon tissues were collected 6, 24 and 72 hours after administration of TNBS. Effects on body weight, gross morphological damage, immune cell infiltration and myenteric neurons were evaluated. RT-PCR, flow cytometry and antibody array kit were used to identify neurotrophic and neuroprotective factors released by MSCs.

Results

MSC and CM treatments prevented body weight loss, reduced infiltration of leukocytes into the colon wall and the myenteric plexus, facilitated repair of damaged tissue and nerve fibers, averted myenteric neuronal loss, as well as changes in neuronal subpopulations. The neuroprotective effects of MSC and CM treatments were observed as early as 24 hours after induction of inflammation even though the inflammatory reaction at the level of the myenteric ganglia had not completely subsided. Substantial number of neurotrophic and neuroprotective factors released by MSCs was identified in their secretome.

Conclusion

MSC-based therapies applied at the acute stages of TNBS-induced colitis start exerting their neuroprotective effects towards enteric neurons by 24 hours post treatment. The neuroprotective efficacy of MSC-based therapies can be exerted independently to their anti-inflammatory effects.

SUBMITTER: Robinson AM

PROVIDER: S-EPMC4580595 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

Neuroprotective Potential of Mesenchymal Stem Cell-Based Therapy in Acute Stages of TNBS-Induced Colitis in Guinea-Pigs.

Robinson Ainsley M AM Miller Sarah S Payne Natalie N Boyd Richard R Sakkal Samy S Nurgali Kulmira K

PloS one 20150923 9

<h4>Background & aims</h4>The therapeutic benefits of mesenchymal stem cells (MSCs), such as homing ability, multipotent differentiation capacity and secretion of soluble bioactive factors which exert neuroprotective, anti-inflammatory and immunomodulatory properties, have been attributed to attenuation of autoimmune, inflammatory and neurodegenerative disorders. In this study, we aimed to determine the earliest time point at which locally administered MSC-based therapies avert enteric neuronal ...[more]

PMID: 26397368

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Project description:Inflammatory bowel diseases (IBD) are a growing health problem worldwide, severely affecting patients' life qualities and life expectancies. Therapeutic options, which are rare and focus on symptoms associated with the disease, suffer from increasing numbers of patients refractory to the established strategies. Thus, in order to generate new therapeutic regimens, the detailed understanding of the pathogenic mechanisms causing IBD is necessary. Histamine is an inflammatory mediator associated with IBD. Four histamine receptors are currently known of which the histamine H4-receptor (H4R) has been shown to possess a pro-inflammatory function in several experimental models of inflammatory diseases, including dextran sodium sulfate (DSS)-induced colitis in mice. No single model reflects the complexity of human IBD, but each model provides valuable information on specific aspects of IBD pathogenesis. While DSS-induced colitis mostly relies on innate immune mechanisms, trinitrobenzene sulfonic acid (TNBS)-induced colitis rather reflects T-cell mechanisms. Consequently, an observation made in a single model has to be verified in at least one other model. Therefore, in the present study we investigated the effect of genetic blockade of H4R-signaling in mice subjected to the model of TNBS-induced acute colitis. We analyzed severity and progression of clinical signs of colitis, as well as histopathologic alterations in the colon and local cytokine production. Genetic ablation of H4R expression worsened clinical signs of acute colitis and histological appearance of colon inflammation after TNBS application. Moreover, TNBS instillation enhanced local synthesis of inflammatory mediators associated with a neutrophilic response, i.e., CXCL1, CXCL2, and interleukin-6. Lastly, also myeloperoxidase concentration, indicative for the presence of neutrophils, was elevated in cola of TNBS-treated mice due to the absence of H4R expression. Our results indicate an anti-inflammatory role of histamine via H4R in TNBS-induced acute neutrophilic colitis in mice, thus questioning the strategy of pharmacological H4R blocked as new therapeutic option for patients suffering from IBD.

Dataset Information

Neuroprotective Potential of Mesenchymal Stem Cell-Based Therapy in Acute Stages of TNBS-Induced Colitis in Guinea-Pigs.

Background & aims

Methods

Results

Conclusion

Publications

Neuroprotective Potential of Mesenchymal Stem Cell-Based Therapy in Acute Stages of TNBS-Induced Colitis in Guinea-Pigs.

Similar Datasets

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