PubReading [77] - Engineering transplantable jejunal mucosal grafts using patient- derived organoids from children with intestinal failure - M. Laween, V. Li et al.

Intestinal failure (IF), following extensive anatomical or functional loss of small intestine (SI), has debilitating long-term consequences on 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 pediatric patient biomaterials and show that patient-derived organoids (PDO) can be expanded efficiently in vitro. In parallel, we generate decellularized human intestinal matrix with intact nanotopography, that forms biological scaffolds. Proteomic and Raman spectroscopy analyses reveal highly analogous biochemical profiles of human SI 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 for up to 2 weeks. Our findings provide proof-of-concept data for engineering patient-specific jejunal grafts for children with IF, ultimately aiding in the restoration of nutritional autonomy. - doi:10.1038/s41591-020-1024-z. - 2020