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Organs-on-a-chip - microphysiological platforms as in vitro models of cardiac and adipose tissue

: Loskill, P.; Mathur, A.; Conklin, B.R.; Stahl, A.; Lee, L.P.; Healy, K.E.


Toxicology letters 258 (2016), pp.S153
ISSN: 0378-4274
ISSN: 1879-3169
European Societies of Toxicology (EUROTOX Congress) <52, 2016, Seville>
Fraunhofer IGB ()

Toxicological screening and drug discovery to date has relied on animal models and conventional cell culture, 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 screening using human disease-specific organ-like cultures in a dish. One promising approach to produce these organ-like structures is the use of microfluidic devices, which can simulate 3D tissue structure and function with microphysiological features. Using microfabrication techniques we have developed two microphysiological platforms (MPSs) that incorporate 3D in vitro models of human cardiac and adipose tissue. Both MPSs consist of three functional components: (i) a tissue culture chamber mimicking geometrical organ-specific in vivo properties; (ii) “vasculature-like” media channels enabling a precise and computationally predictable delivery of compounds (nutrients, drugs); and (iii) “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 cardiac MPS is the first system that combines human genetic background, physiologically relevant tissue structure and “vasculature-like” perfusion. Pharmacological studies using it show half maximal inhibitory/effective concentration values (IC50/EC50) that are more consistent with data from primary tissue references compared to cellular scale studies. The cardiac and adipose MPSs are both extremely versatile and can be applied for toxicological screening as well as fundamental research.