Figure 7

Hypothesized mechanism indicating how the cryopreservation methods affect the immune compatibility of human cardiovascular matrices. Potential effects of CFC and IFC treatments on the human immune response to cardiovascular tissue (vessel or heart valves) are illustrated. After CFC, some tissue cells are apoptotic or necrotic, but the tissue still releases high amounts of cytokines such as IL-6, MCP-1, IL-8, latent TGF-β, and smaller amounts of IL-10. These cytokines lead to a strong activation of blood immune cells. Monocytes and T cells are attracted to the tissue graft, where they can infiltrate or receive signals to proliferate. In contrast, after IFC treatment, tissue cells do not undergo apoptosis or necrosis, but have a diminished metabolic activity. The cytokines IL-6, MCP-1, IL-8, IL-10, and TGF-β are released only in small amounts and TGF-β is secreted in its biologically active form. The decreased levels of cytokine release and the presence of active TGF-β lead to an attenuated activation of immune cells. Particularly, migration and infiltration of T cells and monocytes is reduced and T cell proliferation is blocked, which results in a diminished human immune response to IFC tissue compared to CFC.