Research
Role of E-cadherin in the intestinal stem cell homeostasis and regeneration
Recent research suggests that facilitation of the mucosal healing by intestinal stem cells (ISC) could be a promising alternative target for difficult-to-treat patients with inflammatory bowel disease (IBD). The Wnt/β-catenin-signaling pathway is one of the critical pathways to regulate the ISC homeostasis and regeneration, and it is critically regulated by adherens junctions (AJs). Both ISCs and AJs are well known as critical players during mucosal healing, but there is a lack of studies that identify the role of AJs in ISC homeostasis and regeneration. Thus, in this project, we can reveal a novel function of AJs in ISC homeostasis and regeneration during the pathogenesis of IBD. Specifically, downregulated E-cadherin in 3D or 2D cultured colonoids will disrupt the ISCs homeostasis with reduced cell-cell adhesion and increased proliferation of the ISCs. The inactivation of E-cadherin during regeneration after injury will also enhance aISCs proliferation with increased Wnt target genes and result in improvement of recovery from injury. Our findings can possibly apply to the manipulation of ISCs in the autologous stem cell transplantation approach to promote mucosal healing in patients with IBD.
Role of Mesenchymal Stromal Cells in the Porcine Intestinal Development
The intestinal tract has a considerably immature organ and undergoes substantial changes after birth. Recently, the role of intestinal mesenchymal stromal cells (iMSCs) in regulating intestinal stem cells (ISCs) and their differentiation during development was highlighted. Thus, our aim of this proposed study is to identify the role of iMSCs in their interaction with epithelium during postnatal intestinal development and find novel mechanisms of nutritional factors to improve intestinal health in pigs. This will lead us to investigate how nutrient sources enhance the intestinal development related to MSCs/IECs interactions and enhance our understanding of the mechanistic connections between nutrients and gut health to improve pig growth.
Mechanistic insights into the potentials of human bone marrow mesenchymal stem cells in regulating intestinal homeostasis and injury
The disruption of intestinal homeostasis can cause gastrointestinal disorders, including Crohn’s disease and ulcerative colitis, necessitating novel therapeutic approaches. Human bone marrow mesenchymal stem cells (HBBMSC) have shown promising therapeutic effects by promoting angiogenesis, modulating immune response, and epithelial regenerations. Currently, most studies focused on their immune-modulatory functions, while the underlying mechanisms regulating their epithelial regenerations remain elusive. Could MSCs derived from bone marrow directly influence intestinal epithelial homeostasis and repair processes? To explore cellular interactions between intestinal epithelial cells and HBMMSC, the study will apply novel co-culture models of human colonoid and HBMMSC to elucidate the mechanism of actions influencing colonoid and HBMMSC communications.