Extended Culture of Kidney MPS and Organoids to Model Acute and Chronic Exposure to Drugs and Environmental Toxins

Science Objectives

The Extended Culture of Kidney MPS and Organoids to Model Acute and Chronic Exposure to Drugs and Environmental Toxins investigation will use kidney chips and kidney organoids to better understand kidney injury and recovery from chronic exposure to drugs, toxins, and pathogens. Kidney chips are small credit card-sized devices that contain cells from human kidneys; organoids are tiny collections of cells forming structures that resemble human kidney tissue. The goal is to accelerate the development of better and safer treatments to prevent and potentially identify a cure for kidney diseases.

Graphic showing a transparent credit-card sized device with six blue lines with small blue squares sprouting from the bottom of the device. There are three small red squares in the middle with very thin and small lines connected to them with darker red boxes attached. Beside this device are two microscopic images expanded. They look abstract with blue, green, red and purple colors mixed around with no distinct pattern.
Kidney chip and cultured kidney proximal tubule cells (left) and kidney organoid with multiple self-assembled cell types (right)

Experiment Description

The key to kidney disease prevention and finding kidney disease cures requires innovative strategies and models. The Extended Culture of Kidney MPS and Organoids to Model Acute and Chronic Exposure to Drugs and Environmental Toxins investigation approaches the challenge by developing two innovative models: the proximal tubule epithelial microphysiologic system (MPS) and the iPSC-derived kidney organoid. The goal of this investigation is to extend the use of the systems to model longer exposures to stressors and subsequent recovery to up to 6 months. If successful, researchers can then test functional outcomes of the extended longevity platform after 5 months of exposure to drugs/toxins/diseases and following one month of recovery. Development of increased longevity kidney MPS and organoids will allow better understanding of chronic kidney disease and kidney toxicity/injury to accelerate drug development and provide guidance on strategies to prevent or mitigate nephrotoxicity caused by drugs, environmental chemicals, pathogens, and microgravity.

Space Applications

Kidney health is critical for proper bone density, maintaining body fluid balance, and removing drugs and toxins from the body. Astronauts are at increased risk of kidney problems due to microgravity and unique environmental exposures. This investigation will develop extended longevity cell models that can be used to evaluate the effects of extended space travel on kidney health.

Earth Applications

Successful completion of this project will establish kidney MPS and organoid systems as useful models to better understand the role of chronic stressor exposure on kidney disease initiation progression, and recovery, and will accelerate the discovery and development of new therapeutic agents to treat and prevent kidney diseases.

Team

Principal Investigators

Catherine K. Yeung, PhD
University of Washington, Seattle, Washington, United States

Edward J. Kelly, PhD
University of Washington, Seattle, Washington, United States

Benjamin S. Freedman, PhD
University of Washington, Seattle, Washington, United States

Co-Investigators

Kenneth E. Thummel, PhD
University of Washington, Seattle, Washington, United States

Jonathan Himmelfarb, MD
University of Washington, Seattle, Washington, United States

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