Abstract

Multiorgan Microphysiological Systems as Tools to Study Complex Diseases

Martin Trapecar, Assist. Prof. , JHU

Human multiorgan microphysiological systems (MOMPS) are engineered environments whose purpose is to mimic native cellular surroundings. This is accomplished with the use of tissue-specific biomaterials, machined or printed 3D architecture and perfusion. Controlled interaction of individual human tissues and the scalability of biological complexity in MOMPS, supported by advances in systems biology, might hold the key to identify novel relationships between interorgan crosstalk, metabolism, and immunity. The Trapecar lab is integrating donor-matched tissues into MOMPS to investigate how i) interorgan communication directs complex tissue development and organ-level renewal and how ii) a disruption thereof leads to emergence of immunometabolic pathologies. We show that tissue-level interaction between and within the three main germ layers ectoderm (neurons), mesoderm (lymphoid) and endoderm (gut and liver) leads to increased tissue maturation and increased in vivo-like functionality. In our approach we reconstruct donor-matched hepatic, gut-mucosal and neuronal tissue under fluidic communication and presence of the donors circulating immune cells. We further use the established system to derive how a metabolic disruption in immune-tissue signaling contributes to overlapping inflammatory disorders of the gut-liver-brain axis such as inflammatory bowel disease and neurodegeneration. Paired with multiomic analysis and resolution into molecular underpinnings of cellular and tissue homeostasis, MOMPS represent a unique opportunity to systematically dissect how interactions at a lower order inform new behavior at the macroscale within and between organ systems. Such scalable complexity might yield new insight into fundamental emergence of disease and tissue regeneration.