4th Annual BMRP Investigator Meeting - Abstract
Embryonic Stem Cells Improve Colitis and Decrease IL-12 Levels in the Colitis Mice
Anand S. Srivastavaa, Udai Singh and Ewa Carrierb
Cancer Center, University of California, San Diego (La Jolla, California, U.S.A.)
Evidence suggests a disturbed balance between proinflammatory and anti-inflammatory cytokines in Crohn’s disease (CD). Serum level of IL-12 is significantly elevated in colitis- suffering individuals and animals with colitis. Stem cells, essential for maintaining the tissues integrity of all adult tissues, may provide a foundation for therapeutic advancement in this disease. However, the intestinal stem cells remain enigmatic and no report is available on the transplantation of embryonic stem (ES) cell into an animal model of CD. We have induced murine colitis with piroxicam in IL10-/- knockout (KO) mice by standard protocols and studied effects of the in vitro-predifferentiated embryonic stem cells on intestinal histology and immune balance. These mice display full symptomatology of colitis with typical histological changes and will die unless rescue treatment is provided within several months of induction. We injected 1000 cells/mouse into the tail vein six weeks after induction of colitis. Tissues were obtained three and six months after injection for engraftment studies and ELISA. Our hypothesis was that engrafted ES/epithelial cells will engraft and restore immune balance, ameliorating colitis symptoms, which should be associated with decreased IL-12 levels. Engraftment was detected in the colon and livers of transplanted mice, which correlated with improvement in histology, decreased weight gain and increased activity of surviving mice. Engrafted mice showed marked decrease in IL-12 level, which correlated with the improvement in intestinal histology. The ongoing work focuses on transplant conditions (number of injected ES cells, timing, repeated infusions, use of cytokines, etc.) required to maintain low-levels of IL-12, as well as understanding molecular mechanisms by which embryonic stem cells control colitis.
aCo-investigator and Presenter; bPrincipal Investigator