A human proximal tubule-on-a-chip to study renal disease and toxicity.

Renal disease is a global problem with unsustainable health-care costs. There currently exists a lack of accurate human renal disease models that take into account the complex microenvironment of these tissues. Here, we present a reusable microfluidic model of the human proximal tubule and glomerulus, which allows for the growth of renal epithelial cells in a variety of conditions that are representative of renal disease states including altered glomerular filtration rate, hyperglycemia, nephrolithiasis, and drug-induced nephrotoxicity (cisplatin and cyclosporine). Cells were exposed to these conditions under fluid flow or in traditional static cultures to determine the effects of a dynamic microenvironment on the pathogenesis of these renal disease states. The results indicate varying stress-related responses (α-smooth muscle actin (α-SMA) expression, alkaline phosphatase activity, fibronectin, and neutrophil gelatinase-associated lipocalin secretion) to each of these conditions when comparing cells that had been grown in static and dynamic conditions, potentially indicating more realistic and sensitive predictions of human responses and a requirement for a more complex "fit for purpose" model.

Modeling Barrier Tissues In Vitro: Methods, Achievements, and Challenges.

Organ-on-a-chip devices have gained attention in the field of in vitro modeling due to their superior ability in recapitulating tissue environments compared to traditional multiwell methods. These constructed growth environments support tissue differentiation and mimic tissue-tissue, tissue-liquid, and tissue-air interfaces in a variety of conditions. By closely simulating the in vivo biochemical and biomechanical environment, it is possible to study human physiology in an organ-specific context and create more accurate models of healthy and diseased tissues, allowing for observations in disease progression and treatment. These chip devices have the ability to help direct, and perhaps in the distant future even replace animal-based drug efficacy and toxicity studies, which have questionable relevance to human physiology. Here, we review recent developments in the in vitro modeling of barrier tissue interfaces with a focus on the use of novel and complex microfluidic device platforms.