Utilising nanotopography to maintain pluripotency and differentiate functionally long lived stem cell derived hepatocytes.

Akutt leversvikt er en svært alvorlig tilstand med høy mortalitet uten transplantasjon. Dette forsterkes av både mangelen på organer som kan transplanteres og mangelen på effektive instrumenter som midlertidig kan støtte organfunksjonen, slik man kan bruke dialyse ved nyresvikt. Vår tilnærming er å ta i bruk stamcelleteknologi. Stamceller kan utvikles til alle typer celler som er i kroppen vår. Vi har nylig utviklet en metode for å lage leverceller ved å tilsette kjemikaler til stamceller. Dette er en utvikling fra de tradisjonelle metodene som baserer seg på proteiner. Denne nye metoden reduserer kostnadene ved dyrkning av cellene og dermed kan vi lage et så stort antall leverceller at man kan bruke det i ett instrument for å støtte leverfunksjonen. For å lage så mye leverceller at vi kan bruke det til å støtte leverfunksjonen til en pasient må vi endre måten vi dyrker levercellene på fra flate plastikk skåler til cellesuspensjonsmetoder.

Based on our work, we have been invited to participate in a H2020 application this coming April with Kings college hospital in London. This will be to use our liver organoids to treat paediatric liver failure patients as a proof of principle. In addition, as a consequence of this work I have been invited to participate on the management committee of a european union COST action, on DILI https://www.cost.eu/actions/CA17112/#tabs|Name:overview This has impacted on providing a very important network for tapping into potential EU funding opportunities.

This international collaborative study brings together three innovative research groups with diverse backgrounds & expertise in nanotechnology, materials science, stem cell biology, scale up culture systems, hepatocyte differentiation, toxicology and tissue engineering. These disciplines will be used synergistically, with emerging technologies, to develop both an innovative and ground-breaking platform to provide ´proof of concept´ that can be translated to the clinical setting in terms of bioartifical liver (BAL) device to, disease states, cellular models and toxicology applications. In this proposal we will exploit both the diverse strengths of the assembled team for the fabrication of human pluripotent stem cell derived liver tissue - as an exemplar organotypic model system. Appropriate human hepatic tissue models may more accurately reflect human responses regarding physiological homeostasis, drug metabolism/ toxicity/ safety/ efficacy, disease presentation and importantly provide a platform for the development of a BAL. This proposal is in perfect alignment with the research strategy of the ?STAMCELLER Program? and complements all of the thematic priority areas. The main aim of this project is gain a deeper understanding into the fabrication of a physiologically relevant in vitro model from human pluripotent stem cells, to build modular components for a platform, which recapitulate many aspects of in vivo human liver physiology. A fundamental necessity to advance the current state of BAL devices in acute liver failure providing a stop gap for seriously and chronically ill patients, in addition providing effective tools for disease modelling and drug screening.