Mesenchymal stem cells: a novel therapeutic approach for feline inflammatory bowel disease

Abstract

Background: Inflammatory bowel disease (IBD) poses a significant and growing global health challenge, affecting both humans and domestic cats. Research on feline IBD has not kept pace with its widespread prevalence in human populations. This study aimed to develop a model of feline IBD by incorporating dextran sulfate sodium (DSS) to evaluate the therapeutic potential of MSCs and to elucidate the mechanisms that enhance their action.

Methods: We conducted a comprehensive clinical assessment, including magnetic resonance imaging (MRI), endoscopy, and histopathological examination. Additionally, alterations in intestinal microbiota were characterized by 16 S rDNA sequencing, and the influence of MSCs on IBD-related gene expression was investigated through transcriptome analysis.

Results: According to our findings, MSC treatment significantly mitigated DSS-induced clinical manifestations, reduced inflammatory cell infiltration, decreased the production of inflammatory mediators, and promoted mucosal repair. Regarding the intestinal microbiota, MSC intervention effectively corrected the DSS-induced dysbiosis, increasing the presence of beneficial bacteria and suppressing the proliferation of harmful bacteria. Transcriptome analysis revealed the ability of MSCs to modulate various inflammatory and immune-related signaling pathways, including cytokine-cytokine receptor interactions, TLR signaling pathways, and NF-κB pathways.

Conclusion: The collective findings indicate that MSCs exert multifaceted therapeutic effects on IBD, including the regulation of intestinal microbiota balance, suppression of inflammatory responses, enhancement of intestinal barrier repair, and modulation of immune responses. These insights provide a solid scientific foundation for employing MSCs as an innovative therapeutic strategy for IBD and pave the way for future clinical explorations.

Keywords: Cat model; Inflammatory bowel disease; Intestinal microbiota; Mesenchymal stem cells (MSCs).

Fig. 1

Construction and evaluation of a feline IBD Model. (a) Procedure for the induction of feline IBD-like injury; (b) Body weight monitoring over the experimental period; (c) Fecal scoring system to assess intestinal inflammation; (d) Endoscopic images of the colon showcasing mucosal changes; (e) Magnetic resonance imaging scans of the colon with measurements of mucosal thickness; (f) Histopathological images of colonic tissue illustrating the extent of injury and inflammation. Significant variations had been denoted with * (p < 0.05), ** (p < 0.01), or *** (p < 0.001)

Fig. 2

MSCs improve clinical signs of feline IBD. (a) Feline IBD-like injury treatment procedures; (b) Monitoring of body weight as an indicator of efficacy; (c) Assessment of fecal scores reflecting intestinal health; (d) Endoscopic observation of the colonic mucosa before and after MSC treatment; (e) Histopathological examination of colonic tissues after MSC intervention; (f) Quantitative analysis of serum levels of inflammatory cytokines; (g) Immunohistochemical staining of the colon showing MSCs’ protective effects of MSCs on the intestinal barrier; (h) Expression levels and relative quantification of colonic barrier proteins. Significant variations had been denoted with * (p < 0.05), ** (p < 0.01), or *** (p < 0.001)

Fig. 3

MSCs modulate gut microbiota composition changes induced by feline IBD-like Injury. (a) Alpha diversity indices of the gut microbiota; (b) Beta diversity indices illustrating variations among microbial communities; (c) Taxonomic composition at the phylum and genus levels within the bacterial communities

Fig. 4

MSCs Modulate the Gut Microbiota to Ameliorate Feline IBD-like Injury. (a) Differential bacterial taxa at the phylum and genus levels; (b) Bacterial correlation network analysis. Significant variations had been denoted with * (p < 0.05), ** (p < 0.01), or *** (p < 0.001)

Fig. 5

MSCs Ameliorate Intestinal Transcriptomic Alterations Induced by Feline IBD-like Injury. (a) PCA plot illustrating sample clustering; (b) Heatmap depicting sample correlation coefficients

Fig. 6

MSCs Modulate the Intestinal Transcriptome to Ameliorate Feline IBD-like Injury. (a) Volcano plot depicting differential gene expression; (b) Bubble chart illustrating KEGG enrichment analysis of differentially expressed genes; (c) Statistical analysis of differential gene expression. Significant variations had been denoted with * (p < 0.05), ** (p < 0.01), or *** (p < 0.001)

Fig. 7

Correlation between Gut Microbiota, Intestinal Transcriptome, and IBD-like Injury. (a) Heatmap illustrating the correlation between inflammatory markers and gut bacterial taxa; (b) Heatmap depicting the correlation between inflammatory markers and differentially expressed intestinal genes. Significant variations had been denoted with the aid of * (p < 0.05), ** (p < 0.01), or *** (p < 0.001)