An Experimental Model to Assess Drug Toxicity in the Human Liver

What is it about?

An innovative hybrid microfluidic chip has been developed for the formation, cultivation, and evaluation of hepatocyte spheroids. The chip incorporates a large array of patterned microwells, providing a reproducible and well-organized platform for culturing hepatic spheroids within a dynamic fluidic environment. This device enables the maintenance and characterization of spheroids of different sizes, as well as the simultaneous exposure to various drugs for efficient high-throughput experimentation. Our liver spheroids exhibit physiologically relevant hepatic functionality, as demonstrated by their ability to produce albumin and urea at levels comparable to those observed in vivo. Moreover, the microenvironment of the chip effectively discerns the toxic effects of selected drugs, underscoring its capacity to sustain the functionality of hepatocyte spheroids.

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Why is it important?

In line with the regulatory developments that restrict the use of animal testing and recognizing the evolutionary differences between animal and human physiology and metabolism, there is an increasing research effort to shift drug screening methods from reliance on high-dose animal studies to systems grounded in human biology. This necessitates the development of in vitro models that accurately mimic human organ anatomy and (patho)physiology, and are truly predictive of human response to new drugs. Organoids and spheroids have emerged as the leading representative models of three-dimensional tissue architecture. These models leverage the innate biology of cells to self-assemble into living and functional tissue units, displaying a high level of anatomical and physiological accuracy.

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