Translational center for kidney microphysiological systems to improve drug safety and efficacy

ABSTRACT - Overall The overall goal of the University of Washington Translational center for kidney microphysiological systems to improve drug safety and efficacy is to expand upon kidney tissue chip developmental work our team has accomplished over the past decade, in order to qualify these microphysiological systems as drug development tools for specific Contexts of Use. Despite marked recent advances in our understanding of the physiology and pathophysiology of the human kidney in health and in disease, there are relatively few drugs that are proven to be safe and effective therapies for kidney diseases. Historically, the structural, functional and physiological complexity of the kidney has contributed significantly to the high rate of failures in therapeutic drug development. The complex multicellular architecture and unusual triad of physiological processes characterized by glomerular filtration, tubular secretion and tubular reabsorption, have limited the ability of animal models to recapitulate the diversity of etiologies, mechanisms, and heterogeneous clinical manifestations of most human kidney diseases. The limitations resulting from extrapolating animal model data to human kidney diseases constitutes a major barrier to developing new therapies. Until recently there has been a lack of human in vitro models that recapitulate critical aspects of kidney function or assess reparative mechanisms in response to injury. This is in part because microfluidic flow is so essential to kidney structure and cellular function. In response to this critical unmet need, our group has pioneered the development of ‘human kidney-on-a-chip’ microphysiological systems. Our in vitro on chip models recapitulate critical aspects of kidney physiology, assess the mechanisms and response to injury, and can test reparative mechanisms, all of which can substantially enhance successful drug development that is needed to improve the lives of people living with kidney diseases