Role of Mesenchymal Stem Cells in Intestinal Epithelial Cell Growth​

Abstract

Mucosal healing derived from intestinal epithelial regeneration is crucial in the complete remission of patients with inflammatory bowel diseases (IBDs). Human Bone Marrow Mesenchymal (HBMMSCs) stem cells have been researched as a therapeutic approach to promote mucosal healing through immunomodulation, angiogenesis, and tissue repair. Most preclinical animal studies focus on immune-modulatory functions, but the mechanisms related to epithelial regeneration are poorly understood. We hypothesized that colonoids co-cultured with HBMMSC would increase cell growth and stemness, which are principal for epithelial regeneration. Two different co-culture methods were used: direct and indirect. In the direct method, we analyzed the impact of HBMMSC on colonoid growth and differentiation when the cells were embedded together in Matrigel. In the indirect method, the transwell mimicked the intestine's structure, with the colonoids layered over the HBMMSCs, and isolated each cell type separately to evaluate the gene expression using real-time PCR. Colonoids with HBMMSCs exhibited enhanced stemness and growth, indicated by increased spheroidal surface area and decreased budding counts compared to those without HBMMSCs. Intestinal stem cell genes, like LGR5, ASCL2, and OLFM4, showed a significant increase in the co-cultured cells compared to control cells. We also noted repression of differentiation markers, such as ALPi, IHH, and PTCH1, in co-cultured colonoids. HBMMSCs show promise for promoting mucosal healing in IBD patients by enhancing epithelial regeneration. Yet, further research is needed to understand the repair mechanisms and cellular pathways influenced by HBMMSCs.