Morphological alterations of cultured human colorectal matched tumour and healthy organoids

// Seyed Mohammad Hossein Kashfi 1 , Sheema Almozyan 1 , Nicholas Jinks 1 , Bon-Kyoung Koo 2 and Abdolrahman S. Nateri 1 1 Cancer Genetics & Stem Cell Group, Cancer Biology, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham, UK 2 Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, UK Correspondence to: Abdolrahman S. Nateri, email: a.nateri@nottingham.ac.uk Keywords: colorectal cancer; organoids; intestinal epithelium stem cell; transplantation; personalized medicine Received: July 31, 2017 Accepted: January 09, 2018 Published: January 19, 2018 ABSTRACT Organoids have extensive applications in many fields ranging from modelling human development and disease, personalised medicine, drug screening, etc. Moreover, in the last few years, several studies have evaluated the capacity of organoids as transplantation sources for therapeutic approaches and regenerative medicine. Nevertheless, depending on the origin of the cells and anatomical complications, an organoid transplant may make tissue regeneration difficult. However, some essential aspects of organoids including the morphological alterations and the growth pattern of the matched tumour and their healthy derived organoids have received less attention. Therefore, the current work focused on culturing matched healthy and tumour organoids from the same patient with colorectal cancer (CRC) and assessed their timed growth and structural differences on a daily basis. The healthy organoids underwent proliferation and branching morphogenesis, while the tumour organoids did not follow the same pattern, and the majority of them developed cystic structures instead. However, the number and size of tumour organoids were different from one patient to another. The differential morphological changes of the healthy versus human colonic tumour organoids likely linked to distinct molecular and cellular events during each day. Thus, while their specific structural features provide valuable in vitro models to study various aspects of human intestinal/colon tissue homeostasis and CRC which avoid or replace the use of animals in research, this model may also hold a great promise for the transplantation and regenerative medicine applications.