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Organovo: 3D printed liver tissue to challenge current toxicity models

By Dan Stanton+

20-Aug-2014
Last updated on 20-Aug-2014 at 16:35 GMT

'3D printed heads' but Organovo's printing platform uses real cells to create living tissue for preclinical testing
'3D printed heads' but Organovo's printing platform uses real cells to create living tissue for preclinical testing

A 3D printed human liver system could offer better informed risk-based decisions earlier in the drug development process than with current in vitro models, according to developers Organovo.

3D printing has already infiltrated the pharma world, with the NIH launching a service to recreate laboratory equipment and molecular models , and NASA hoping to print pills in space . Now the preclinical industry is being targeted by San Diego-based Organovo, which is using its 3D NovoGen Bioprinting technology to build liver tissue that can be used in ADME (absorption, distribution, metabolism, and excretion) and Toxicology testing.

The liver models are made using three cell types - primary hepatocytes, endothelial cells, and hepatic stellates - which are expanded and specially prepared into a ‘printable’ bioink, Executive Vice President Michael Renard explained to Outsourcing-Pharma.com.

“These materials are loaded onto the bioprinter and delivered in a precise x,y,z orientation as programmed and controlled by the printer software,” he continued. “The printed tissues are then conditioned… enabling the design and creation of fully functioning, 3D tissue models with precise and reproducible architecture.”

These ‘living’ liver tissues can be used for various types of ADME and Toxicology testing, and offer advantages over the cultured bacteria or mammalian cells currently used for in vitro profiling, according to Renard.

“The tissue provides the ability to measure analytical protein, gene expression, histologic, toxicological and metabolic endpoints with greater physiological relevance than traditional cell and tissue models over an extended in vitro lifespan,” he said, adding “this is the only system today that persists as long as 40 days without loss of phenotypic function.”

The platform is being used to evaluate the toxicity of the pain relief compounds diclofenac and acetaminophen “and so far has seen expected responses at effective concentrations lower than observed in other models,” he said.

Partnering

The technology has also received a boost from drug giant Roche, which recently presented data on its ability to distinguish between two structurally similar compounds that have very different toxic profiles.

For now Organovo is focusing on providing evidence that supports the model improving the efficiency of the drug discovery process, and hopes to attract interest from a pharma or CRO technology partner.

If fruitful, Renard said the 3D model could provide “a new level of relevance and predictive value from an in vitro model,” while “better informing risk based decisions earlier in the process.”

‘Body-building’ technology

There are other opportunities beyond liver tissue for Organova’s 3D printing platform, Renard said, with the firm having already used the technology to print kidney, skin, lung, and blood vessel tissue models.

“This technology is ideally suited for developing disease models where composition and architectural orientation matter in achieving representative function,” we were told. “A prime example of this is in the creation of soft tissue cancerous tumour models.”

Last month, Organovo entered into an agreement with Janssen Research and Development (JRD ) in order to evaluate the use of 3D bio-printed tissue in a drug discovery setting outside of the Company’s work in 3D liver tissue for toxicity testing. No further details have been made available at this stage.

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