Reduction of animal experiments through in-vitro modelling of multi-organ interactions
Many experimental therapies never reach the clinic because of unwanted side-effects or lack of therapeutic effects in animals or Phase-I clinical trials. To better predict these factors in the lab, this project will use a multi-organ-on-a-chip system to investigate the interaction between extracellular vesicle therapy and different organs in diabetic nephropathy.
With the aging population and Western lifestyle, diabetes and diabetes-associated diseases are rising to epidemic proportions. Diabetic nephropathy results from chronic diabetes, and is the leading cause of end-stage kidney disease. Great social and economic burden associated with kidney diseases urge for novel therapies. Stem cell-based regenerative medicine, including stem cell-derived extracellular vesicles (EV), may provide such therapies. For development and subsequent human translation of these therapies, representative animal models are indispensable to gain comprehensive understanding on molecular mechanisms and potential (unwanted, indirect) effects in off-target organs. However, testing candidate therapies in animals is expensive, time-consuming, and associated with ethical concerns. Reduction of animals by stringent pre-selection of potential therapies is therefore needed. Based on recent developments in microfluidics (TissUse), 3D organoid culturing and EV biology (UMC Utrecht), they will develop a human “Multi-Organ-on-a-Chip” platform combining kidney, liver and pancreas physiology. As diabetic nephropathy originates from a systemic disease, such a system is excellently suited to assess therapeutic efficacy of EV-based regenerative therapies in a systemic environment.
To this end, this project will develop a chip-based model functionally combining liver, pancreas and kidney proximal physiology in health and disease. In this model, experimental EV-based therapy will be applied, and functional and molecular effects in each organ will be evaluated.
