Heart-on-a-chip beats a steady rhythm

Posted: March 12, 2015 at 1:45 pm

The growing number of biological structures being grown on chips in various laboratories around the world is rapidly replicating the entire gamut of major human organs. Now one of the most important of all a viable functioning heart has been added to that list by researchers at the University of California at Berkeley (UC Berkeley) who have taken adult stem cells and grown a lattice of pulsing human heart tissue on a silicon device.

Sourced from human-induced pluripotent stem cells able to be persuaded into forming many different types of tissue, the human heart device cells are not simply separate groups of cells existing in a petri dish, but a connected series of living cells molded into a structure that is able to beat and react just like the real thing.

"This system is not a simple cell culture where tissue is being bathed in a static bath of liquid," said study lead author Anurag Mathur, a postdoctoral researcher at UC Berkeley. "We designed this system so that it is dynamic; it replicates how tissue in our bodies actually gets exposed to nutrients and drugs."

Touted as a possible replacement for living animal hearts in drug-safety screening, the ability to easily access and rapidly analyze a heart equivalent in experiments presents appealing advantages.

"Ultimately, these chips could replace the use of animals to screen drugs for safety and efficacy," said professor of bioengineering at UC Berkeley, and leader of the research team, Kevin Healy.

The cardiac microphysiological system, as the team calls its heart-on-a-chip, has been designed so that its silicon support structure is equivalent to the arrangement and positioning of conjoining tissue filaments in a human heart. To this supporting arrangement, the researchers loaded the engineered human heart cells into the priming tube, whose cone-shaped funnel assisted in aligning the cells in a number of layers and in one direction.

In this setup, the team created microfluidic channels on each side of the cell holding region to replicate blood vessels to imitate the interchange of nutrients and drugs by diffusion in human tissue. The researchers believe that this arrangement may also one day provide the ability to view and gauge the expulsion of metabolic waste from the cells in future experiments.

"Many cardiovascular drugs target those channels, so these differences often result in inefficient and costly experiments that do not provide accurate answers about the toxicity of a drug in humans," said Professor Healy. "It takes about US$5 billion on average to develop a drug, and 60 percent of that figure comes from upfront costs in the research and development phase. Using a well-designed model of a human organ could significantly cut the cost and time of bringing a new drug to market."

The use of animal organs to forecast human reactions to new drugs is problematic, the UC Berkeley researchers note, citing the fundamental differences between species as being responsible for high failure rates in using these models. One aspect responsible for this failure is to be found in the difference in the ion channel structure between human and other animals where heart cells conduct electrical currents at different rates and intensities. It is the standardized nature of using actual human heart cells that the team sees as the heart-on-a-chip's distinct advantage over animal models.

The UC Berkeley device is certainly not the first replication of an organ-on-a-chip, but potentially one of the first successful ones to integrate living cells and artificial structures in a single functioning unit. Harvard's spleen-on-a-chip, for example, replicates the operation of the spleen, but does so by using a set of circulatory tubes containing magnetic nanobeads.

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Heart-on-a-chip beats a steady rhythm

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