Humanized NSG Mouse Models as a Preclinical Tool for Translational Research in Inflammatory Bowel Diseases

• Published in: International journal of molecular sciences 2023-08, Vol.24 (15), p.12348
• Main Authors: Weß, Veronika, Schuster-Winkelmann, Paula, Karatekin, Yasemin Hazal, Malik, Simge, Beigel, Florian, Kühn, Florian, Gropp, Roswitha
• Format: Article
• Language: English
• Subjects: animal models; B cells; Collagen; Colon; Correlation analysis; Crohn's disease; Disease; Disease susceptibility; Edema; Ethanol; Fibroblasts; Gastrointestinal diseases; IBD; immune-deficient; Immunology; Inflammation; Inflammatory bowel disease; Leukocytes; Medical research; Medicine, Experimental; mouse models; Patients; Scientific equipment and supplies industry; T cells; Transforming growth factors
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms241512348

The development of animal models reflecting the pathologies of ulcerative colitis (UC) and Crohn's disease (CD) remains a major challenge. The NOD/SCID/IL2rγ (NSG) mouse strain, which is immune-compromised, tolerates the engraftment of human peripheral blood mononuclear cells (PBMC) derived from patients with UC (NSG-UC) or CD (NSG-CD). This offers the opportunity to examine the impact of individual immunological background on the development of pathophysiological manifestations. When challenged with ethanol, NSG-UC mice exhibited a strong pro-inflammatory response, including the development of edemas, influx of human T cells, B cells and monocytes into the mucosa and submucosa, and elevated expression of the inflammatory markers CRP and CCL-7. Fibrotic alterations were characterized by an influx of fibroblasts and a thickening of the muscularis mucosae. In contrast, the development of pathological manifestations in NSG-CD mice developed without challenge and was signified by extensive collagen deposition between the muscularis propria and muscularis mucosae, as observed in the areas of strictures in CD patients. Vimentin-expressing fibroblasts supplanting colonic crypts and elevated expression of HGF and TGFß corroborated the remodeling phenotype. In summary, the NSG-UC and NSG-CD models partially reflect these human diseases and are powerful tools to examine the mechanism underlying the inflammatory processes in UC and CD.