Human-relevant Drug Discovery Pipeline Using Non-animal Models

The adoption of non-animal models (NAMs) for drug and product safety assessment is rapidly gaining momentum among regulatory agencies and pharmaceutical companies worldwide. Integrating human pluripotent stem cell (hPSC) technology with microfluidic microphysiological systems (MPS) holds tremendous promise for replicating heterotypic tissue interactions critical to human physiology and disease; paving the way for innovative avenues in drug discovery. In this talk, I will share our work on developing hPSC-derived MPS platforms that model individual tissues, such as the heart, liver, and pancreatic islets, highlighting their application in drug toxicity screening and discovery, including the use of artificial intelligence to accelerate drug development and repurposing. I will then discuss our progress in engineering a multi-organ MPS model for type 2 diabetes mellitus (T2DM), integrating hPSC-derived adipocytes, hepatocytes, macrophages, and islet-β cells. This section will focus on strategies for common medium formulation, system scaling, and recapitulating key metabolic signatures at the onset of T2DM, such as hepatic insulin resistance triggered by adipocyte inflammation. Finally, I will introduce our efforts to create digital twins of pancreatic islets and address current challenges and emerging solutions in developing robust NAMs for translational research and drug discovery.