We are delighted to report that in the last months we have achieved very important results. In particular, some significant research outcomes have been published in Nature and Nature Medicine. The implication of these results is so relevant to the field that Nature Medicine decided to run an editorial on the topic. Also Nature Review Gastroenterology and Hepatology wrote an article on this topic.
To summarise the most recent findings reported in these 2 papers:
1) We constructed autologous jejunal mucosal grafts using biomaterials from paediatric patients affected by SBS and showed that patient-derived organoids can be expanded efficiently in vitro. In parallel, we generated decellularized human intestinal matrix maintaining the intact structure and composition of the biological scaffolds. We could reveal that profiles of human small intestine and colon scaffolds are very similar, indicating that they can be used interchangeably as platforms for intestinal engineering. This opens up the possibility of using the residual colon as scaffolding in children who have lost the entire small bowel. Indeed, seeding of jejunal organoids onto either type of scaffold reliably reconstructs grafts that exhibit several aspects of physiological jejunal function. We were also able to transplant them in vivo and demonstrate they can survive to form luminal functional structures for a short time. These findings provide proof-of-concept data for engineering patient-specific jejunal grafts for children with intestinal failure, ultimately aiding in the restoration of nutritional autonomy.
2) Using tissue engineering and the intrinsic self-organization properties of cells, we induced intestinal stem cells to form tube-shaped epithelia with an accessible lumen and a similar spatial arrangement of crypt- and villus-like domains to that in vivo. When connected to an external pumping system, the mini-gut tubes are perfusable; this allows the continuous removal of dead cells to prolong tissue lifespan by several weeks, and also enables the tubes to be colonized with microorganisms for modelling host–microorganism interactions. The mini-intestines include rare, specialized cell types that are seldom found in conventional organoids. They retain key physiological hallmarks of the intestine and have a notable capacity to regenerate. Our concept for extrinsically guiding the self-organization of stem cells into functional organoids-on-a-chip is broadly applicable and will enable the attainment of more physiologically relevant organoid shapes, sizes and functions.