PMC:6141714 / 101140-104292 JSONTXT

{"project":"MyTest","denotations":[{"id":"30254638-12507163-35421656","span":{"begin":655,"end":658},"obj":"12507163"},{"id":"30254638-16635908-35421657","span":{"begin":896,"end":899},"obj":"16635908"},{"id":"30254638-9029093-35421658","span":{"begin":1315,"end":1318},"obj":"9029093"},{"id":"30254638-27087453-35421659","span":{"begin":1418,"end":1421},"obj":"27087453"}],"namespaces":[{"prefix":"_base","uri":"https://www.uniprot.org/uniprot/testbase"},{"prefix":"UniProtKB","uri":"https://www.uniprot.org/uniprot/"},{"prefix":"uniprot","uri":"https://www.uniprot.org/uniprotkb/"}],"text":"Celiac disease is an autoimmune inflammatory enteropathy caused by the ingestion of gluten in genetically susceptible individuals. Ingestion of gluten by these patients results in a chronic inflammatory response in the mucosa of the small intestine, which is accompanied by atrophy of the villi and hyperplasia of the intestinal crypts. The clinical manifestations of the celiac disease are very variable, and the patients affected by the disease may be asymptomatic, manifest symptoms of intestinal malabsorption or extraintestinal manifestations such as dyspepsia, fatigue, infertility, neurological diseases, osteoporosis and dermatitis herpetiformis (203). In patients affected by the celiac disease, the passage of gliadin peptides by the intestinal submucosa through transferrin receptors CD71 acts by activating CD4+ T lymphocytes, which recognize these peptides through T cell receptors (204). As a result, a stimulation of a Th1 and/or Th2 type response occurs, culminating in the secretion of pro-inflammatory cytokines such as IL-15, IFN-γ, IL-17, IL-21, and IL-23, which damage the intestinal mucosa. The secretion of IFN-γ stimulates fibroblasts to secrete metalloproteinases, which act degrading the collagen, glycoproteins and proteoglycans of the extracellular matrix, resulting in villous atrophy (205). The treatment of type II refractory celiac disease was carried out with hMSCs in only one study (118), which used the bone marrow as the source of hMSCs and was conducted in humans. This study was a single case report and used the stool frequency, the change in mucosal architecture, and the percentage of body weight change as the primary endpoints that were applied in order to assess the efficacy of hMSCs administration for the treatment of celiac disease. Celiac disease, like other food and allergy-related disorders, lacks well-defined clinical endpoints. Therefore, we recommend that multiple endpoints should be combined to capture the overall activity of the disease. Possible endpoints that can be used in combination includes: intestinal permeability, histological scores, gluten concentration, villus-height-to-crypt-depth ratio and changes in the levels of biomarkers in the serum. Exploratory endpoints such as the serum levels of cytokines and the proportion of inflammatory cells in the blood can be used to assess the immunomodulatory potential of the hMSCs administration. In the study selected, a reduction in the severity of the disease was observed after the administration of hMSCs. In particular, treatment with hMSCs resulted in a full macroscopic and microscopic recovery of the gut mucosa, and, as a consequence, in the normalization in stool frequency and a decrease in the weight loss resulting from the disease. Finally, an accentuated reduction in the levels of both IL-15 cytokine and IL-15 receptor at the mucosal level were observed after hMSCs treatment. Table 5 summarizes the methodology employed and the results obtained in the studies selected in this systematic review regarding the effects of the administration of hMSCs for the treatment of chronic inflammatory disorders of the intestine."}

{"project":"2_test","denotations":[{"id":"30254638-12507163-35421656","span":{"begin":655,"end":658},"obj":"12507163"},{"id":"30254638-16635908-35421657","span":{"begin":896,"end":899},"obj":"16635908"},{"id":"30254638-9029093-35421658","span":{"begin":1315,"end":1318},"obj":"9029093"},{"id":"30254638-27087453-35421659","span":{"begin":1418,"end":1421},"obj":"27087453"}],"text":"Celiac disease is an autoimmune inflammatory enteropathy caused by the ingestion of gluten in genetically susceptible individuals. Ingestion of gluten by these patients results in a chronic inflammatory response in the mucosa of the small intestine, which is accompanied by atrophy of the villi and hyperplasia of the intestinal crypts. The clinical manifestations of the celiac disease are very variable, and the patients affected by the disease may be asymptomatic, manifest symptoms of intestinal malabsorption or extraintestinal manifestations such as dyspepsia, fatigue, infertility, neurological diseases, osteoporosis and dermatitis herpetiformis (203). In patients affected by the celiac disease, the passage of gliadin peptides by the intestinal submucosa through transferrin receptors CD71 acts by activating CD4+ T lymphocytes, which recognize these peptides through T cell receptors (204). As a result, a stimulation of a Th1 and/or Th2 type response occurs, culminating in the secretion of pro-inflammatory cytokines such as IL-15, IFN-γ, IL-17, IL-21, and IL-23, which damage the intestinal mucosa. The secretion of IFN-γ stimulates fibroblasts to secrete metalloproteinases, which act degrading the collagen, glycoproteins and proteoglycans of the extracellular matrix, resulting in villous atrophy (205). The treatment of type II refractory celiac disease was carried out with hMSCs in only one study (118), which used the bone marrow as the source of hMSCs and was conducted in humans. This study was a single case report and used the stool frequency, the change in mucosal architecture, and the percentage of body weight change as the primary endpoints that were applied in order to assess the efficacy of hMSCs administration for the treatment of celiac disease. Celiac disease, like other food and allergy-related disorders, lacks well-defined clinical endpoints. Therefore, we recommend that multiple endpoints should be combined to capture the overall activity of the disease. Possible endpoints that can be used in combination includes: intestinal permeability, histological scores, gluten concentration, villus-height-to-crypt-depth ratio and changes in the levels of biomarkers in the serum. Exploratory endpoints such as the serum levels of cytokines and the proportion of inflammatory cells in the blood can be used to assess the immunomodulatory potential of the hMSCs administration. In the study selected, a reduction in the severity of the disease was observed after the administration of hMSCs. In particular, treatment with hMSCs resulted in a full macroscopic and microscopic recovery of the gut mucosa, and, as a consequence, in the normalization in stool frequency and a decrease in the weight loss resulting from the disease. Finally, an accentuated reduction in the levels of both IL-15 cytokine and IL-15 receptor at the mucosal level were observed after hMSCs treatment. Table 5 summarizes the methodology employed and the results obtained in the studies selected in this systematic review regarding the effects of the administration of hMSCs for the treatment of chronic inflammatory disorders of the intestine."}