Grant: Operating Grant

Whether you have a heart attack, a stroke, liver transplant, a hit on the head, or drug induced toxicity, there is a repair process that takes place. Much like knocking down an old house to build a new one, when vasculature and tissue is injured, immune cells enter, kill everything and allow for rebuilding of new blood vessels and tissues. However, killing injured cells when they cannot be replaced can lead to worsening of injury rather than repair and one can develop a scar. We have a special microscope that allows us to visualize the entire process from injury, to inflammation to repair and track the different cell types that contribute to this process. We can thermally injury a tiny area of the liver tissue and vasculature and within one week the tissue is completely repaired. This will not happen in other types of liver injury, meaning something special happens that lets the liver fully repair. First, neutrophils enter the site and seem to allow for blood vessels to start growing, then monocytes come in and they help clear the debris and then magically switch to a repair cell. We know if we prevent either cell from getting into the inflammatory site, injury is either impaired or a scar forms. Scars unfortunately are plan B when repair cannot occur and result in dysfunctional tissue. Understanding these events in this very simple system where there is complete healing, will help us to understand why sometimes disrepair occurs and how we might be able to therapeutically intervene.