A model system for primary abdominal closures

The foreign body response to medical devices and materials implanted in the human body, including scarring, fibrous encapsulation, and potential rejection, is a longstanding and serious clinical issue. There are no widely acceptable or safe therapies for ameliorating the foreign body response. Clinical complications resulting from the response include disfigurement of silicone prostheses and loss of function of devices such as implanted pacemakers, stents, and shunts. Cellularized implants and stem cells placed in the body are also subject to the foreign body response with the added issue that the regenerative repair intended to be prompted by the graft may be inhibited. Beneficial modification of the body's reaction to implanted materials, medical devices, engineered constructs, or stem cells would be a fundamentally important therapeutic advance. As part of investigating the cellular response, we have developed a model which uses cells isolated from skeletal muscle biopsy, cultured, and proliferated in vitro. These satellite cells, which are mononucleated progenitor cells, reside between the plasma membrane of the muscle fiber and the basal membrane that encompasses the fiber. While usually quiescent, these cells become activated following muscle damage. Once activated, the satellite cells proliferate, migrate to injured muscle, and participate in repair by fusing with existing muscle fibers or by differentiating into new skeletal muscle fibers. Satellite cells have been shown to be heterogeneous populations of stem cells and progenitor cells. We have developed an explant method for isolating, sorting, enriching, and culturing these cells for use in skeletal muscle regenerative medicine to determine if the foreign body response can be inhibited by manipulating the cell-cell communication.