A method of inducing ischemia includes: providing a cell culture device having a first cell culture in an internal chamber and a second cell culture in at least one fluid channel and a perfusion modulating system that causes changes in oxygen flow in the internal chamber and/or at least one fluid channel; flowing liquid media having oxygen through the internal chamber and at least one fluid channel of the cell culture device; modulating oxygen perfusion in the internal chamber with the perfusion modulating system by varying and selectively blocking the flow rate of at least one of the liquid media or oxygen through the internal chamber to induce varying levels of ischemia; and assaying for ischemia in the first cell culture.