Human proliferative hepatocyte organoids developed by HUB
Recently, Hu et al, from the Hubrecht Institute developed proliferative hepatocyte organoids (Hep-Orgs), distinct from cholangiocyte derived organoids (Chol-Orgs).
Building on this work, an elegant study by Yang et al was conducted in a collaboration between Sauerwein lab at Radboud Center of Infectious Diseases, Radboud University Medical Center, and Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences, The Netherlands. Well-characterised defined hepatocyte organoids were used to give a unique insight into life cycle of the Plasmodium parasite in host cells and was combined with single cell transcriptomics to generate an informative non-biased dataset.
As an example of utility, the authors highlight the discovery of a later functional role in parasite development for SR-B1, already known to be involved in early phases. Intriguingly, this unique window on biological mechanism appeared parasite strain independent, suggesting that liver organoid model systems, combined with transcriptomics, have promise for the elucidation of new malarial drug targets and opportunities for determination of drug mechanism.
The next steps for this technology, and a challenge many organoid platforms are facing, is how to effectively scale the technology to establish an organoid-based drug target identification platform. As we see these systems scale and become standardized, this opens opportunities to build further biological complexity into organoid models and deploy CRISPR to begin to develop an understanding of human hepatocyte host cell factors.