Engineered Multi-Tissue Platform for Modeling Systemic Human Pathologies

Bioengineered tissue platforms offer a new paradigm for modeling human pathophysiology and testing drug efficacy and safety. At present, establishing physiological communication between multiple tissues while preserving their individual phenotypes remains a major challenge that must be overcome to model whole-body physiology and systemic diseases. Toward this goal, we developed the biomimetic InterOrgan platform in which matured human tissues are connected in a way that allows maintaining distinct functionalities of different organs (e.g. heart, liver, bone, skin). Each tissue is cultured in its own optimized environment and separated from the recirculating vascular flow containing monocytes, by a matured and selectively permeable endothelial barrier. Tissues linked by vascular perfusion maintained their molecular, structural, and functional phenotypes over four weeks of culture, recapitulated multi-organ toxicity of doxorubicin observed in pediatric and adult clinical studies, and enabled identification of clinically relevant early miRNA biomarkers of cardiotoxicity. Additionally, the platform shows utility for immune-oncology applications as circulating tumor cells preferentially extravasate to expected metastatic sites and myocardial cryoinjury studies demonstrate immune infiltration to the site of injury. Overall, the InterOrgan platform can facilitate clinical translation by enabling physiologic communication of phenotypically stable engineered human tissues.