A Bioreactor to Apply Multimodal Physical Stimuli to Cultured Cells

Cells residing in the cardiac niche are constantly experiencing physical stimuli, including electrical pulses and cyclic mechanical stretch. These physical signals are known to influence a variety of cell functions, including the secretion of growth factors and extracellular matrix proteins by cardiac fibroblasts, calcium handling and contractility in cardiomyocytes, or stretch-activated ion channels in muscle and non-muscle cells of the cardiovascular system. Recent progress in cardiac tissue engineering suggests that controlled physical stimulation can lead to functional improvements in multicellular cardiac tissue constructs. To study these effects, aspects of the physical environment of the myocardium have to be mimicked in vitro. Applying continuous live imaging, this protocol demonstrates how a specifically designed bioreactor system allows controlled exposure of cultured cells to cyclic stretch, rhythmic electrical stimulation, and controlled fluid perfusion, at user-defined temperatures.