Read about Krauss' research and innovation project
Predictability and reproducibility are key factors in ensuring confidence in results in pharmaceutical research. The development of drugs commonly uses animal models to test drug efficacy, toxicity and metabolism, among others, however, animals are different than humans and may lead to results that are not directly translatable.
Organ-on-chip technology is a term used for microfluidic systems that enable the cultivation and culture of living cells in a way that resembles aspects of the histology and functionality of organs.
The cells used in an organ-on-chip platform are either derived from stem cells or taken from patient material. When coupled to perfusion they function as laboratory-grown organ representations. Organ-on-chip systems ultimately aim to provide better models for the human physiology of a given organ, when used in drug discovery.
Addressing the issues of current model organ-on-chip models
According to Stefan Krauss, despite the promising possibilities of the current organ-on-chip models, there are still multiple issues that need to be resolved.
Central issues are that current stem cell-derived organ representations lack the complexity of a mature organ at a physiological and histological level, and they are often functionally immature.
– Not having the complex, histological structure and functional maturity makes it difficult to copy the functions of a mature organ. Functional immaturity can e.g. be observed in the sense that these structures are not representing the metabolic capability of an adult. Liver organoids for example show a metabolic activity that is more at a fetal level than a postnatal or even adult level.
Krauss adds that the interplay of the organ representations with the immune system can be an important factor in certain disease conditions which is currently difficult to model in organ-on-chip systems. These issues hamper to a certain degree the value of these models.
– There is also a lot of variation between batches and experiments which further hinders its applicability and reproducibility in an industrial or clinical setting. Overall, organ-on-chip platforms have complexity challenges that need to be resolved. Organ-on-chip platforms that are currently used in the field are either very simple or extremely complicated with a lot of tubing reducing reproducibility and scaling. We therefore develop a “mezzanine” platform that is both easily scalable yet allows to include complexity beyond what is commonly seen in scalable platforms, he explains.
Better models for more reproducible research
Krauss and his team, including Mathias Busek and Aleksandra Aizenshtadt, are working towards addressing the above-mentioned challenges of microphysiological systems.
– Our solution is to have a simple scalable system which we call the revolving organ-on-chip system or rOoC. The system is based on a circular liquid flow without the need of tubing or integrated pump actuators. This allows to reach a level of complexity that is higher when compared to standard commercial platforms, and at the same time both robust and scalable.
This will hopefully result in higher reproducibility and less variability between experiments, and hence fulfil a central requirement of the pharmacological industry, says Krauss.
In terms of developing organoids, the group is developing robust protocols in particular for liver organoids that show a higher degree of metabolic maturity compared to published organoids.
– The liver organoids are still relatively simple structures compared to a mature liver sinusoid, but the developed protocol can have a value in the market, says Krauss.
Collaboration with industry
Krauss and his team are collaborating with several national and international partners on their organoid and organ-on-chip technology. One of the promising collaborations is with Oncosyne AS, a Norwegian startup that is working on personalised drug testing in cancer. Krauss hopes to continue these collaborations to assembling expertise both at PhD, postdoctoral and supervisory level to further advance the development of microphysiological systems towards commercial applications.
– Ongoing animal testing could one day be replaced by microphysiological systems, given that they have the potential to be better and more predictive in a human personalized setting than current animal models, says Krauss.
Still early days for organoid research
According to Krauss, the pharmacological industry is very interested in exploring a microphysiological system like organoids and organ-on-chip systems. Large pharmaceutical companies from around the world are investing in collaborating with academic laboratories, startup companies, and some companies also develop such systems in-house to test their capacity and to build up working platforms.
– We have already seen cases where drug recommendations for patients are based on tests made on organoids. In particular in the cancer area, patient-derived tumour organoids are already quite broadly used to guide therapeutic recommendations in a variety of clinical trials, says Krauss.
He adds that it is, however, still early days for the development of microphysiological systems and most companies are still in an exploratory phase as the systems need to be carefully tested, validated and standardised before they can be put into commercial use.
Read about the collaboration with the UiO Growth House and the innovation journey ahead
Krauss collaboration with UiO’s innovation unit the UiO Growth House with regard to the organ-on-chip technology started after they received seed funding from the Growth House spring 2022.
– Discussions with the UiO Growth House have been very encouraging. We and the UiO Growth House share some of the same pragmatic philosophy on the importance of cultivating innovation and startup development at the university, says Krauss.
– As I understand, the UiO Growth House wants to enable innovation by creating the possibility of combining academia and innovation – an important feature for many startup companies. Venturing into developing a startup comes along with many risks as many of these start-ups may fail at some stage. A permissive and flexible environment that enables to do innovative work while still having academic security is important for creating a vivid startup culture,
Krauss and his team have received innovation funding from the University of Oslo, Oslo University Hospital and the Research Council of Norway. In addition, several projects in the HTH centre have been admitted to UiO:Life Science’s innovation programme the SPARK Norway.
Now Krauss and his colleagues intend to draft a Centre of Research Based Innovation proposal to bridge academic research, start-ups and large pharmaceutical companies and create an environment that is driven to do more innovative work.
A pilot for pilot sale
Krauss and the UiO Growth House have also discussed the possibility of a pilot sale of the chip platforms through the UiO prior to incorporation of a startup. Such a system would help to generate value before venturing into the operational setup of a company. This, however, has not been implemented yet as Krauss and his team including Mathias Busek and Aleksandra Aizenshtadt are still optimising the organ-on-chip technology.
For the UiO Growth House these discussions have however laid the ground for working with general processes and agreements for pilot sale in the UiO Growth House, thus also benefitting other research groups at the university that are considering this possibility.