Bringing a human heart & fat on a chip: Microphysiological platforms as in vitro models of cardiac and adipose tissue

Drug discovery and development to date has relied on animal models, which are useful, but fail to resemble human physiology. The discovery of human induced pluripotent stem (iPS) cells has led to the emergence of a new paradigm of drug screening using human disease-specific organ-models. One promising approach to produce these systems is employing microfluidic devices, which can simulate 3D tissue structure and function. Using microfabrication techniques we have developed two microphysiological platforms (MPSs) that incorporate in vitro models of human cardiac and adipose tissue. Both MPSs consist of three functional components: a tissue culture chamber mimicking geometrical organ-specific in vivo properties; ""vasculature-like"" media channels enabling a precise and computationally predictable delivery of compounds (nutrients, drugs); ""endothelial-like"" barriers protecting the tissues from shear forces while allowing diffusive transport. Both organ-chips are able to create physiological micro-tissues that are viable and functional for multiple weeks. The developed chips are the first systems that combine human genetic background, physiologically relevant tissue structure and ""vasculature-like"" perfusion. Pharmacological studies on the heart-chip show IC50/EC50 values more consistent with data from primary tissue references compared to cellular scale studies. Both MPSs are extremely versatile and can be applied for drug toxicity screening and fundamental research.