RGM.20.002 – LymphChip: Developing immunocompetent human organ-on-a-chip models with integrated lymph drainage for drug discovery and testing

Route: Regenerative medicine: game changer moving to broad areas of application

Cluster question: 100 How can we use cells, stem cells, and biomaterials to engineer and regenerate tissues and organs?

The lymphatic system plays a crucial role in our immune system, for example by regulating the immune response to pathogens. Lymphatic dysfunction underlies a multiplicity of diseases, and could determine the effectiveness of therapies, whether drug or stem-cell based. Yet, in the new generation of in-vitro organ models used to study the effect of drugs and therapies without the need for animals, the lymphatic system and the immune cells they transport are notably absent. The fact that the lymphatics of human organs are significantly different from those of animals like mice, and ethical concerns about animal use combine to an urgent need for human-physiologically relevant organotypic models that include human lymph-endothelial and immune cells. In LymphChip, pioneers of the organ-on-chip platform join forces to develop these models for the first time.

Starting from proven stem cell-derived models of three organ systems (heart, intestine, and skin), we will develop innovative combinations of microengineered biomimetic 3D scaffolds, miniaturized interstitial flow models and on-line sensing, integrating primary and stem cell-derived tissues and corresponding tissue lymphatics. We will thus create powerful models for studying tissue homeostasis via fluid transport (for the heart), small molecule and dietary fat transport (intestine) and immune surveillance (for skin and lymph nodes). This will provide unprecedented opportunities for studying human disease in which the lymphatic system is defective by providing personalized, patient-specific immune systems in near-native tissue environments with stromal and immune cell components and real-time measures of function.

Our ambition is to provide game-changing technology to address presently intractable conditions of the immune system using three tissues as exemplars that will lead the way towards the identification of novel pathways for these and other organs while reducing animal use.

Keywords

Human, immune cells, Lymphatics, Organ-on-a-chip, Pluripotent stem cells

Submitter

Organisation Leiden University Medical Center (LUMC)
Name Dr. V. (Valeria) Orlova
E-mail v.orlova@lumc.nl
Website www.lumc.nl