Engineering transplantable jejunal mucosal grafts using patient-derived organoids from children with intestinal failure
Authors listLaween Meran Isobel Massie Sara Campinoti Anne Weston Riana Gaifulina Lucinda Tullie Peter Faull Michael Orford Ania Kucharska Anna Baulies Domenech Laura Novellasdemunt Vilaseca Nikos Angelis Elizabeth Hirst Julia König Alfonso Maria Tedeschi Alessandro Filippo Pellegata Susanna Eli Bram Snijders Lucy Collinson Nikhil Thapar Geraint MH Thomas Simon Eaton Paola Bonfanti Paolo De Coppi Vivian Li
Intestinal failure, following extensive anatomical or functional loss of small intestine, has debilitating long-term consequences for children1. The priority of patient care is to increase the length of functional intestine, particularly the jejunum, to promote nutritional independence2. Here we construct autologous jejunal mucosal grafts using biomaterials from pediatric patients and show that patient-derived organoids can be expanded efficiently in vitro. In parallel, we generate decellularized human intestinal matrix with intact nanotopography, which forms biological scaffolds. Proteomic and Raman spectroscopy analyses reveal highly analogous biochemical profiles of human small intestine and colon scaffolds, indicating that they can be used interchangeably as platforms for intestinal engineering. Indeed, seeding of jejunal organoids onto either type of scaffold reliably reconstructs grafts that exhibit several aspects of physiological jejunal function and that survive to form luminal structures after transplantation into the kidney capsule or subcutaneous pockets of mice for up to 2 weeks. Our 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.
Journal Nature Medicine
Issue number 10