Figure 9.

Action of dextran sulfate sodium in immunodeficient mice and role of administration of umbilical cord mesenchymal stem cells in colitic mice. (A) Mechanism of action of DSS in immunodeficient mice and (B) role of administration of umbilical cord mesenchymal stem cells (UCMSCs) in colitic mice. Dextran sulfate sodium (DSS) administration in immunodeficient mice induces integrin degradation, matrix metalloproteinase (MMP) activation and endoplasmic reticulum (ER) stress. These events induce increased epithelial apoptosis and the imbalance between apoptosis and proliferation, causing relevant leaks in the epithelial barrier, with consequent inflammation. Infiltrating neutrophils and macrophages produce reactive oxygen species (ROS) that lead to cell death and further tissue damage. Moreover, ROS is one of the important stimuli that triggers ER stress. All of these events involving MMP activation and ER stress presumably lead to the establishment of colitis with clinical signs comparable with inflammatory bowel diseases in humans, but without the participation of T lymphocytes, B lymphocytes and natural killer cells. UCMSCs administration in colitic mice is able to reduce MMP and ER activation, resulting in less epithelial degradation and inflammation. Consequently, ROS production is lower and the vicious cycle of epithelial damage is inhibited. In this way, UCMSCs are able to prevent DSS-induced colitis. MSC, mesenchymal stem cell.