Described herein is a microphysiological
system for models of
disease. Specifically, induced pluripotent stem cells (iPSCs) and iPSC-derived cells, including those obtained from
disease patients, are seeded onto microfluidic “
chip” devices to study
cellular development and
disease pathogenesis. Herein, neurodegenerative disease modeling, including Parkinson's
Disease (PD) is shown to reproduce key PD
pathology in a vascularized human model that contains neurons relating to PD
pathology. Such compositions and methods are used for research for PD biomarkers,
patient screening for PD
risk assessment, and therapeutic discovery and testing. A panel of biomarkers are generated through analysis of living PD-chips by
neural activity, whole transcriptomic, proteomic, and metabolomic analysis, and functional
enzyme tests of media and tissue. Introducing therapeutics through a vasculature channel, coupled with
blood brain barrier penetration studies can be assessed for
efficacy in the human neural cells present in the PD-
Chip.