Miniaturised organ equivalents for drug testing

Dr Reyk Horland, VP Business Development of TissUse, speaks to Angharad Baldwin of Manufacturing Chemist about a powerful new tool that has the potential to predict toxicity or efficacy early on in the drug development process

To imitate the complex processes occurring in the body, TissUse has developed organ-on-a-chip technology to emulate multiple human organs interacting on a device the area of a microscope slide. It is anticipated that this technology will make it possible to clarify how humans react to new medications or chemicals and significantly reduce the need for animal testing.

The microfluidic platform can maintain miniaturised human organ equivalents to incorporate the crucial features of living biological systems, such as pulsatile fluid flow, mechanical and electrical coupling, physiological tissue-to-fluid and tissue-to-tissue ratios.

The chip includes a cell culture compartment, adapter plates, a polydimethylsiloxane layer and a glass slide. Cells, tissues and organ models can be cultured within the cell culture compartment on the chip. The compartments are interconnected by microfluidic channels in a similar way that organs within the body are interconnected by vasculature, allowing researchers to mirror physiologically relevant organ functions to substance exposure at a previously unprecedented level.

“Multi-organ-chip and, especially, body-on-a-chip systems give researchers the opportunity to investigate the effects of substances at a systemic level in vitro. Currently, this can only be done in animal models; and, in animals, the phylogenetic differences between species must be taken into account,” says Horland.

“The technology from TissUse can be used as a powerful new tool to predict toxicity or efficacy early in the drug development process. Multi-organ chip systems have the potential to generate data that, so far, has only been possible in animal studies or clinical trials,” he adds.

The multi-organ chip is based on a modular concept. “As of now, we have established 13 single organ models on the platform. Based on these models, 12 different organ combinations for various applications in pharma, biotech, cosmetics and the chemical industry have been developed. These organ combinations are also used to model a variety of diseases on the platform,” comments Horland. The miniaturised human multi-organ systems are capable of generating crucial data during the preclinical assessment of drug candidates and are expected to improve drug development success rates. Recently, TissUse collaborated with AstraZeneca to explore the unmet need for a physiologically relevant human ex-vivo type 2 diabetes model. The result, based on insulin and glucose regulation, was a human microfluidic two-organ chip model to study the cross-talk between pancreatic islets and the liver for up to 15 days.

“There is great potential for the innovative multi-organ chip technology to enhance our approaches to drug development. Our collaboration with TissUse enabled us to utilise the technology to advance our understanding of the biological control in key unmet disease areas such as type 2 diabetes,” says Dr Regina Fritsche-Danielson of AstraZeneca.

All organ models and organ combinations are designed to be cultivated on the chip in homeostasis for up to 28 days. Developing organ models and organ combinations for prolonged periods of time gives the opportunity for repeated dose application regimens. Testing can either be performed on ‘healthy’ organ models or combinations for safety assessment or on ‘diseased’ organ models or combinations for safety and efficacy testing. Fully physiologically based pharmacokinetic-compliant chip systems are currently under development, expected to launch later this year, and could then be used for ADME-T modelling.

TissUse is also aiming to establish iPS-derived organ models on the chip. This will allow for the selection of different genotypic backgrounds when testing the safety of substances and for patient specific disease modelling.

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