Keynote Message

The development of organoid cultures by the lab of Hans Clevers (Hubrecht Institute) is considered a major scientific breakthrough. Since their first publication in 2009 on mouse 'mini-guts,' organoids have gained a massive amount of attention from both academia and clinic, but also from the media. Organoids are defined as 'structures resembling an organ' and have already been created from for example intestine, liver, pancreas, and stomach tissue. The 3D culture is based on specific medium components that drive proliferation of adult tissue-specific stem cells and as a result allow for a culture of primary cells with impressive expansion capacity. Organoids were first derived from mouse and then from human (patient-) samples. In collaboration with the Hubrecht Institute our lab has established organoid cultures from dog and cat liver (Nantasanti et al. 2015; Kruitwagen et al. 2017) and dog intestine (Conceicao Meneses et al. manuscript in preparation). Organoids have already proved to be a valuable tool for disease modeling research (e.g., in human cystic fibrosis) and are also considered for transplantation purposes. But the question arises how far we are from actual clinical application and how also veterinary medicine can benefit from organoid development. Currently, our lab is performing a transplantation study of autologous canine liver organoids in dogs with genetic copper storage disease. A second project is the culture of feline liver organoids and their application as preclinical disease model for hepatic lipidosis. A third study focuses on canine intestinal organoids to model viral enteritis. In this session, the potential and limitations of organoids will be discussed using examples from previous publications and examples from own experience.

Key References

1.  Sato T, Vries RG, Snippert HJ, van de Wetering M, Barker N, Stange DE, van Es JH, Abo A, Kujala P, Peters PJ, Clevers H. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature. 2009;459:262–5. DOI: 10.1038/nature07935.

2.  Huch M, Dorrell C, Boj SF, van Es JH, Li VS, van de Wetering M, Sato T, Hamer K, Sasaki N, Finegold MJ, Haft A, Vries RG, Grompe M, Clevers H. In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration. Nature. 2013;494:247–50. DOI: 10.1038/nature11826.

3.  Kruitwagen HS, Spee B, Viebahn CS, Venema HB, Penning LC, Grinwis GCM, Favier RP, van den Ingh TSGAM, Rothuizen J, Schotanus BA. The canine hepatic progenitor cell niche: molecular characterisation in health and disease. The Veterinary Journal. 2014;201:345–52. DOI: 10.1016/j.tvjl.2014.05.024.

4.  Kruitwagen HS, Spee B, Schotanus BA. Hepatic progenitor cells in canine and feline medicine: potential for regenerative strategies. BMC Veterinary Research. 2014;10:137. DOI: 10.1186/1746-6148-10-137.

5.  Nantasanti S, Spee B, Kruitwagen HS, Chen C, Geijsen N, Oosterhoff LA, van Wolferen ME, Pelaez N, Fieten H, Wubbolts RW, Grinwis GC, Chan J, Huch M, Vries RRG, Clevers H, de Bruin A, Rothuizen J, Penning LC, Schotanus BA. Disease modeling and gene therapy of copper storage disease in canine hepatic organoids. Stem Cell Reports. 2015;5:895–907. DOI: 10.1016/j.stemcr.2015.09.002.

6.  Kruitwagen HS, Oosterhoff LA, Vernooij IGWH, Schrall IM, van Wolferen ME, Bannink F, Roesch C, van Uden L, Molenaar MR, Helms JB, Grinwis GCM, Verstegen MMA, van der Laan LJW, Huch M, Geijsen N, Vries RG, Clevers H, Rothuizen J, Schotanus BA, Penning LC, Spee B. Long-term adult feline liver organoid cultures for disease modeling of hepatic steatosis. Stem Cell Reports. 2017;8:822–830. DOI: 10.1016/j.stemcr.2017.02.015