Significant progress toward creating ‘benchtop human’ reported

Scientists are reporting significant progress toward creating “homo minutus” — a benchtop human.

Researchers have successfully developed and analyzed a liver human organ construct that responds to exposure to a toxic chemical much like a real liver.

The advance — successful development and analysis of a liver human organ construct that responds to exposure to a toxic chemical much like a real liver — was described in a presentation by John Wikswo, the Gordon A. Cain University Professor and Director of the Vanderbilt Institute for Integrative Biosystems Research and Education (VIIBRE) at Vanderbilt University.

The achievement is the first result from a five-year, $19 million multi­ institutional effort led by Rashi Iyer, senior scientist at Los Alamos National Laboratory (LANL), and Wikswo. The project is developing four interconnected human organ constructs — liver, heart, lung and kidney — that are based on a highly miniaturized platform nicknamed ATHENA (Advanced Tissue-engineered Human Ectypal Network Analyzer). The project is supported by the Defense Threat Reduction Agency. Similar programs to create smaller, so-called organs-on-chips are underway at the Defense Advanced Research Projects Agency and the National Institutes of Health.

“The original impetus for this research comes from the problems we are having in developing new drugs,” said Wikswo. “A number of promising new drugs that looked good in conventional cell culture and animal trials have failed when they were tested in humans, many due to toxic effects. That represents more than $1 billion in effort down the drain. Our current process of testing first in cell lines on plastic and then in mice, rats and other animals simply isn’t working.”

In recent years, a cadre of scientists and clinicians around the world has begun to develop more relevant and advanced laboratory tests for drug efficacy and toxicity: small bioreactors that can form human organ structures and are equipped with sensors to monitor organ health.

Ultimately, the goal is to connect the individual organ modules chemically in a fashion that mimics the way the organs are connected in the body, via a blood surrogate. The ATHENA researchers hope that this ”homo minutus,” with its ability to simulate the spatial and functional complexity of human organs, will prove to be a more accurate way of screening new drugs for potency and potential side-effects than current methods.

Devices of this type could also be extremely useful in the field of toxicology. Of the tens of thousands of chemical compounds being used routinely in commerce today, only a small fraction has been tested for toxicity. And even those have been examined only for acute toxicity, not for sub-lethal or chronic effects, because of the expense and time required by such tests. Human organ construct/organ-on-a-chip technology could make this process substantially cheaper and faster.

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